peroxisome function, biogenesis, and - plant physiology · peroxisome function, biogenesis, and...

Update on Plant Peroxisomes

Peroxisome Function Biogenesis andDynamics in Plants1[OPEN]

Yun-Ting Kao2 Kim L Gonzalez2 and Bonnie Bartel3

Department of Biosciences Rice University Houston Texas 77005

ORCID IDs 0000-0003-3163-1238 (YTK) 0000-0003-2961-3081 (KLG) 0000-0002-6367-346X (BB)

Eukaryotic cells employ organellar compartmen-talization to increase efficiency of cellular processesand protect cellular components from harmful pro-ducts such as reactive oxygen species Peroxisomesare organelles that sequester diverse oxidative reac-tions and play important roles in metabolism reactiveoxygen species detoxification and signaling Oxida-tive pathways housed in peroxisomes include fattyacid b-oxidation which contributes to embryogene-sis seedling growth and stomatal opening Otherperoxisomal enzymes enable photorespiration whichincreases photosynthetic efficiency Peroxisomes con-tribute to the synthesis of critical signaling moleculesincluding the jasmonic acid auxin and salicylic acidphytohormones Peroxisomes lack DNA peroxisomalproteins are encoded in nuclear DNA and posttransla-tionally enter the organelle Recent studies have begunto fill gaps in our understanding of how peroxisomalproteins are imported regulated and degraded De-spite this progress much remains to be learned abouthow peroxisomes originate from the ER divide andare degraded through pexophagy a form of organelle-specific autophagy Peroxisomes play vital roles inmultiple aspects of plant life and in this review wehighlight recent advances in our understanding ofplant peroxisome functions biogenesis and dynamicswhile pointing out areas where additional studies areneeded

PEROXISOME FUNCTIONS

Fatty Acid b-Oxidation Not Just for Seedlings

Peroxisomes house fatty acid b-oxidation the pro-cess by which fatty acids are catabolized into acetyl-CoA (Fig 1) Fatty acyl-CoA esters are transportedinto the peroxisome by the ATP-dependent transporter

PEROXISOMAL ABC TRANSPORTER1 (PXA1)COMATOSEPEROXISOME DEFECTIVE3 (PED3)(Zolman et al 2001 Footitt et al 2002 Hayashi et al2002 Nyathi et al 2010) Curiously the fatty acyl-CoAester is hydrolyzed during transport (De Marcos Lousaet al 2013) and then resynthesized inside the organelle(Fulda et al 2004) Once in the peroxisome fatty acyl-CoAs are b-oxidized by the sequential action of threeenzymes each encoded in a small gene family in Arabi-dopsis (Arabidopsis thaliana) acyl-CoA oxidase (ACX1to ACX6) multifunctional protein [MFP2 ABNORMALINFLORESCENCEMERISTEM (AIM1)] and 3-ketoacyl-CoA thiolase (KAT1 KAT2PED1 and KAT5) Thiolasegenerates acetyl-CoAanda chain-shortened fatty acyl-CoA

1 The authorsrsquo peroxisome research is funded by the National In-stitutes of Health (R01GM079177) the National Science Foundation(MCB-1516966 to BB DGE-0940902 to KLG) and the Robert AWelch Foundation (C-1309)

2 These authors contributed equally to the article3 Address correspondence to bartelriceeduY-TK KLG and BB wrote the article and prepared the figures[OPEN] Articles can be viewed without a subscriptionwwwplantphysiolorgcgidoi101104pp1701050

162 Plant Physiology January 2018 Vol 176 pp 162ndash177 wwwplantphysiolorg 2018 American Society of Plant Biologists All Rights Reserved wwwplantphysiolorgon October 15 2020 - Published by Downloaded from

Copyright copy 2018 American Society of Plant Biologists All rights reserved

which can undergo additional b-oxidation roundsSeedling acetyl-CoA is further metabolized by peroxi-somal glyoxylate cycle enzymes into four-carbon dicar-boxylic acids which ultimately can be converted to Sucused for growth (for review see Graham 2008) Perox-isomes are the sole site of fatty acid b-oxidation in plants(for review see Graham 2008) and mutations in thegenes encoding PXA1 various b-oxidation enzymes orglyoxylate cycle enzymes confer seedling growth defectsthat are partially alleviated by providing a fixed carbonsource such as Suc (for review see Bartel et al 2014)MFP2 andAIM1 requireNAD+which is imported by thePXN peroxisomal NAD+ carrier and recycled by peroxi-somal NAD+-malate dehydrogenase (PMDH) and mon-odehydroascorbate reductase (MDAR4) Consequentlypmdh mdar4 and pxn mutants also display b-oxidationdefects (Eastmond 2007 Pracharoenwattana et al 2007Bernhardt et al 2012 Rinaldi et al 2016 van Roermundet al 2016)Oil bodies also known as lipid droplets compart-

mentalize neutral lipids and allow storage of largequantities of triacylglycerol in oilseeds (for review seePyc et al 2017) During germination and early seedlinggrowth peroxisomes associate with oil bodies (Chapmanand Trelease 1991 Hayashi et al 2001) to utilize seedenergy reserves (for review see Graham 2008) Oil bodytriacylglycerol is hydrolyzed to free fatty acids by the li-pase SUCROSEDEPENDENT1 (SDP1) (Eastmond 2006)which is delivered from peroxisomes to oil bodies withthe assistance of the Golgi retromer complex (Thazar-Poulot et al 2015) The fatty acyl-CoA transporter PXA1

also promotes peroxisome-oil body interactions (Cui et al2016) possibly facilitating peroxisomal invaginations dur-ing oil body consumption

Seedlings retain oil bodies when b-oxidation is im-paired Various mutants defective in b-oxidation theglyoxylate cycle or NADH reduction display peroxi-somes clustered near oil bodies after oil bodies are de-pleted in wild type (Germain et al 2001 Eastmond2007 Pracharoenwattana et al 2007 Cassin-Ross andHu 2014 Rinaldi et al 2016) Moreover diphenylmethylphosphonate confers triacylglycerol retention(Brown et al 2013) similar to sdp1 and pxa1 mutants(Eastmond 2006 Slocombe et al 2009 Kelly et al2013) The mechanism through which peroxisomal en-zyme dysfunction feeds back to prevents triacylglycerolmobilization is unknown

In addition to fueling germination oil bodies andperoxisomes collaborate to provide energy in leavesArabidopsis CGI-58 a homolog of a mammalian lipaseactivator (comparative gene identification-58) promotesPXA1 function in leaves but not in germinating seeds(Park et al 2013) and triacylglycerol accumulates in leafoil bodies in cgi-58 mutants (James et al 2010) More-over b-oxidation of triacylglycerol from stomatal oilbodies contributes to the ATP production necessary forstomatal opening upon transfer from dark to light(McLachlan et al 2016) When b-oxidation is slowed asin pxa1 sdp1 or cgi-58 mutants stomatal opening isimpeded (McLachlan et al 2016) Because environmentalstimuli such as light and temperature regulate stomatalaperture to control water and gas exchange (for review

Figure 1 Plant peroxisome functionsPeroxisomes house a variety of catabolicand biosynthetic reactions (Reumannand Bartel 2016) several of whichgenerate H2O2 and other ROS (orange)b-oxidation (red) is used to catabolizefatty acids (purple) and in the synthesisof several hormones (blue) PeroxisomalROS can be inactivated by catalase andotherenzymeswithin theperoxisomeorcanexit the peroxisomes to serve signaling rolesOPC83-oxo-2-(29-pentenyl)-cyclopentane-1-octanoic acidOPDA12-oxo-phytodienoicacid

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see Hetherington and Woodward 2003) b-oxidation-mediated stomatal opening hints that peroxisomes havea role in responding to environment cues

b-oxidation is also important during embryogenesisArabidopsis pxa1mutants and RNA interference (RNAi)lines targeting barley PXA1 homologs have small seeds(Mendiondo et al 2014) and Arabidopsis doublemutants defective in both multifunctional enzymes orseveral acyl-CoA oxidase isozymes die during embry-ogenesis (Rylott et al 2003 Fulda et al 2004 Khanet al 2012) It is not known if acetyl-CoA or a differentb-oxidation product (Fig 1) is needed for embryogen-esis or if b-oxidation promotes embryogenesis by pre-venting buildup of toxic compounds such as free fattyacids

The interplay between peroxisomal b-oxidation rolesin providing usable fixed carbon and removing toxicfree fatty acids is apparent in the multifaceted rela-tionship between peroxisomal b-oxidation and abioticstress survival The transcripts encoding thiolase andACX4 accumulate during carbon-starvation (Charltonet al 2005 Contento and Bassham 2010) implying thatfatty acid b-oxidation increases upon nutrient depri-vation Indeed several b-oxidation mutants includingpxa1 and mutants with reduced thiolase activity dieprematurely in extended darkness (Dong et al 2009Kunz et al 2009) Both pxa1 and sdp1 mutants catabo-lize triacylglycerol inefficiently in extended darknessbut sdp1 lowers free fatty acid accumulation and ame-liorates plant death in dark-treated pxa1 mutants (Fanet al 2017) implying that free fatty acid toxicity ratherthan carbon starvation contributes to pxa1 death In-triguingly sdp1 survives extended darkness better thanwild type (Fan et al 2017) hinting that triacylglycerolcan protect cells from darkness-induced damage

Reactive Oxygen and Nitrogen Species Not Just forCell Death

The oxidative reactions harbored in peroxisomesgenerate hydrogen peroxide (H2O2) and other reactiveoxygen species (ROS) In addition to theACXb-oxidationenzymes glycolate oxidases (GOX1 to GOX5) acting inphotorespiration and xanthine oxidase acting in uricacid production contribute substantial peroxisomalH2O2 and superoxide radicals (for review see Del Riacuteoand Loacutepez-Huertas 2016) Peroxisomes counter thisROS accumulation using catalase and ascorbate per-oxidase pathways which decompose H2O2 into waterand molecular oxygen Catalase (cat) mutants displayelevated H2O2 and associated transcriptional changesdiminished growth increased cell death (Queval et al2007) and sensitivity to carbon-starvation (Contento andBassham 2010) Suppressor screens for increased pho-tosystem II efficiency in a cat2 mutant recovered ashort-root mutant with decreased photorespiration flux(Waszczak et al 2016) and a gox1mutant (Kerchev et al2016) confirming photorespiratory GOX as a majorH2O2 contributor

Catalase has a particularly close relationship with theH2O2-generating ACX enzymes For example CAT3and ACX4 activity and transcripts are both elevated bycarbon-starvation (Contento and Bassham 2010) More-over cat2 mutants display decreased ACX activity (Liuet al 2017 Yuan et al 2017) and overexpressing ACX3rescues cat2 seedling growth defects (Liu et al 2017) Thefinding that ACX activity is limiting for cat2 growth im-plies that ACX enzymes suffer damage when catalase isdysfunctional Indeed CAT2 physically interacts withand increases activity of ACX3 and ACX4 in vitro (Yuanet al 2017) presumably catalase-ACX proximity allowsrapid inactivation of ACX-generated H2O2

In addition to ROS peroxisomes generate reactivenitrogen species (RNS) after application of stressorssuch as salt or heavy metals (for review see Corpaset al 2017) This accumulation suggests that like ROSRNS could function in stress signaling The peroxisomalNADP-isocitrate dehydrogenase (pICDH) regeneratesNADPH which is used by the peroxisomal ascorbate-glutathione H2O2-inactivating system picdhmutants failto open stomates upon transfer to light unless treatedwith H2O2- or NO-scavenging chemicals (Leterrier et al2016) highlighting a role for peroxisomes inRNS-mediatedenvironmental responses and providing a second exampleof peroxisomes influencing stomatal openingAdditionallyseveral peroxisomal enzymes are nitrosylated includingcatalase GOX and PMDH (for review see Corpas et al2017) which could represent RNS-mediated regulationIt will be interesting to learn the biological roles of RNSandwhether RNS signals are antagonistic or agonistic toROS signaling

b-Oxidation Not Just for Fatty Acids

Beyond fatty acid b-oxidation peroxisomal enzymesb-oxidize precursors of the hormones auxin jasmonicacid (JA) and salicylic acid (SA Fig 1) Indole-3-butyricacid (IBA) one of several auxin precursors in plants (forreview see Korasick et al 2013) is converted in per-oxisomes to the active auxin indole-3-acetic acid (IAAZolman et al 2000 Strader et al 2010 reviewed inStrader and Bartel 2011) IBA-derived auxin is impor-tant during seedling development when it influenceslateral rooting (Zolman et al 2001 De Rybel et al2012) cotyledon and root hair expansion and apicalhook formation (Strader and Bartel 2009 Strader et al2010 2011)

The JA precursor 12-oxo-phytodienoic acid undergoesreduction and two b-oxidation rounds in peroxisomes toyield JA (Fig 1) which functions in reproductive devel-opment and during wound and defense responses (forreview see Wasternack and Hause 2013) For example amaize peroxisomal JA-modifying enzyme controls sexdetermination (Hayward et al 2016) Moreover wound-ing increases ACX1 and PED1 transcript levels (CruzCastillo et al 2004) andArabidopsis acx1 aim1 and ped1mutants fail to produce JA afterwounding (CruzCastilloet al 2004 Delker et al 2007)

164 Plant Physiol Vol 176 2018

Kao et al


Like auxin the defense hormone SA has multiplebiosynthetic pathways SA can be produced in chloro-plasts (for review see Dempsey and Klessig 2017) orafter peroxisomal b-oxidation of transcinnamic acid tothe SAprecursor benzoic acid (Fig 1) Illuminated by thepioneering work on benzoic acid biosynthesis in petunia(van Moerkercke et al 2009 Klempien et al 2012Qualley et al 2012) this pathway was elucidated inArabidopsis Cytosolic transcinnamic acid presumablyas the CoA ester is imported by PXA1 (Bussell et al2014) Inside the peroxisome cinnamoyl-CoA is resyn-thesized (Lee et al 2012) andb-oxidized to benzoyl-CoA(Bussell et al 2014) which is presumably hydrolyzed tobenzoic acid and exported to the cytosol where benzoicacid is converted to SA (Yalpani et al 1993) A rice(Oryza sativa) aim1mutant displays elevated redox geneexpression small root meristems and short roots thatare rescued by treatment with SA or ROS but not JA orauxin suggesting that SA promotes rice root growth viaROSproduction and blocking redox gene expression (Xuet al 2017) These findings illustrate the variedmeans bywhich b-oxidation contributes to ROS and illuminate aROS signaling role in plantsIn addition to hormone production the peroxisome

is a site of hormone cross talk For example SA whichis induced in response to biotrophic pathogens directlyinhibits catalase activity (Yuan et al 2017) This cata-lase inhibition reduces JA production via the conse-quent reduction in ACX activity and reduces IAAproduction through H2O2-mediated modification of akey IAA biosynthetic enzyme (Yuan et al 2017) ThusSA exploits peroxisomal pathways to mediate appro-priate responses to biotrophic pathogens by down-regulating the hormones (JA and IAA) that promoteresponses to necrotrophic pathogens

Photorespiration Not Just for Chloroplasts

In addition to the core processes of b-oxidation andROS detoxification plant peroxisomes house diversespecialized functions (for review see Reumann andBartel 2016) that may change during development(Titus and Becker 1985 Nishimura et al 1986 Sautter1986 Lingard et al 2009) or in response to environ-mental cues (for review see Goto-Yamada et al 2015)For example plant peroxisomes sequester enzymes act-ing in photorespiration which is important when ribu-lose-15-bisphosphate carboxylaseoxygenase fixes O2instead of CO2 As a result high CO2 levels improvegrowth of photorespiratory-deficient plants (for reviewsee Timm and Bauwe 2013) During photorespirationperoxisomal and mitochondrial enzymes collaborate toconvert glycolate from the chloroplast to glycerate to bereturned to the chloroplast for the Calvin cycle Afterentering the peroxisome glycolate is oxidized byGOX toyield glyoxylate and H2O2 (for review see Bauwe et al2010) As seedlings mature photorespiration increasesand the glyoxylate cycle diminishes and glyoxylate istransaminated to Gly which is converted to Ser in the

mitochondrion Ser returns to the peroxisome and isconverted to glycerate by Serglyoxylate aminotransfer-ase and hydroxypyruvate reductase (HPR) HPR de-pends on the NADH provided by PMDH (for reviewsee Bauwe et al 2010)

The impaired growth of catalase mutants is amelio-rated by high CO2 (Queval et al 2007) again impli-cating photorespiratory GOX as a primary H2O2 sourcein leaf peroxisomes Knocking down both GOX1 andGOX2 confers growth defects in ambient air accompa-nied by decreased photosynthetic electron transfer andcarbon assimilation glycolate accumulation and earlysenescence (Dellero et al 2016) Moreover hpr1 mu-tants display not only decreased photosynthetic effi-ciency but also drought sensitivity (Li and Hu 2015)linking peroxisomal photorespiration roles to droughttolerance

PEROXISOME GENESIS

Membrane Protein Insertion and Budding from the ER

Peroxisomes are assembled and maintained by per-oxin (PEX) proteins The early acting peroxins PEX3PEX16 and PEX19 (Fig 2) help insert peroxisomalmembrane proteins (PMPs) directly into the peroxi-somal membrane (group II PMPs) or into a peroxisome-destined region of the ERmembrane (group I PMPs forreview see Hu et al 2012) PEX16 recruits the PEX3membrane protein to the ER in mammals (Kim et al2006) Neurospora PEX3 enlists PEX19 a farnesylatedcytosolic protein to chaperone nascent PMPs to PEX3for membrane insertion (Chen et al 2014) Yeast PMPsbind PEX19 via a membrane peroxisome-targetingsignal a hydrophobic motif near the transmembranedomain (Rottensteiner et al 2004) similar sequencesare found in plant PMPs (Nyathi et al 2012)

In addition to PMP insertion yeast PEX3 and PEX19are implicated in budding of ER-derived preperox-isomal vesicles (van der Zand et al 2010) carrying dis-tinct PMP assortments (Agrawal et al 2016) Moreovermammalian PEX3 can be inserted into themitochondrialouter membrane and mitochondrion-derived preper-oxisomal vesicles can fuse with PEX19-containing ER-derivedpreperoxisomal vesicles to form import-competentperoxisomes (Sugiura et al 2017)

Much remains to be discovered about peroxisomebiogenesis in plants Like in mammals ArabidopsisPEX16 is delivered to the peroxisome via the ER whereit recruits other PMPs (Hua et al 2015) ArabidopsisPEX16 RNAi lines display large peroxisomes andslightly impaired b-oxidation (Nito et al 2007) and aninsertional pex16 allele displays severe embryonic de-fects (Lin et al 1999) Arabidopsis has two isoforms ofPEX3 and PEX19 Single pex19 insertional alleles lackobvious defects whereas a pex19a pex19b double mutantis embryo-lethal indicating functional redundancy(McDonnell et al 2016) PEX3 or PEX19 RNAi linesdisplay large peroxisomes but wild-type b-oxidation(Nito et al 2007) The composition organellar origins




and fusion mechanisms of plant preperoxisomal vesi-cles remain to be elucidated

Peroxisome Division and Proliferation

In addition to budding from the ER peroxisomes candivide by fission (Fig 2) Plant peroxisomes proliferateduring cell division (Lingard et al 2008) and in responseto salinity (Mitsuya et al 2010 Fahy et al 2017) light(Desai andHu 2008) andcadmiumtreatments (Rodriacuteguez-Serrano et al 2016) Division involves the PMP PEX11whichhasfive isoforms (a to e) inArabidopsis (LingardandTrelease 2006) Although decreasing PEX11 expressionvia RNAi does not notably impact b-oxidation or ma-trix protein import Arabidopsis pex11 RNAi lines (Nitoet al 2007 Orth et al 2007) and moss pex11 mutants(Kamisugi et al 2016) exhibit enlarged peroxisomes sug-gesting a conserved division role Additionally PEX11ais implicated in forming peroxisomal membrane exten-sions called ldquoperoxulesrdquo (Rodriacuteguez-Serrano et al 2016)Peroxule formation is induced by ROS (Sinclair et al2009 Rodriacuteguez-Serrano et al 2016) and may promotethe peroxisomal elongation that precedes division(Fig 2) Furthermore loss of PEX11a decreases catalaseand superoxide dismutase gene expression linking ROSsignaling and peroxisomal division (Rodriacuteguez-Serranoet al 2016)

After elongation several proteins collaborate to dividethe peroxisome (Fig 2) The Arabidopsis paralogs ofyeast FISSION1 (Kemper et al 2008) FIS1A and FIS1Bare tail-anchored membrane proteins acting in both mi-tochondrial and peroxisomal fission (for review see Huet al 2012) Knocking down FIS1A and FIS1B decreasesperoxisome numbers in protoplasts (Lingard et al2008) and insertional fis1a alleles display larger and

fewer peroxisomes (Zhang and Hu 2009) and mito-chondria (Scott et al 2006) than wild type

The dynamin-related proteins DRP3A DRP3B andDRP5B are GTPases that like FIS1 are required fordivision of multiple organelles DRP3 functions inperoxisomal and mitochondrial fission whereas DRP5Bsupports fission of peroxisomes and chloroplasts (forreview see Hu et al 2012) Arabidopsis drp3a anddrp3b mutants both display larger and fewer mito-chondria but only drp3a displays larger and fewerperoxisomes (Mano et al 2004 Fujimoto et al 2009Zhang and Hu 2009) coupled with slight b-oxidationdefects (Mano et al 2004) Overexpressing DRP3B butnot DRP3A causes peroxisome elongation (Fujimotoet al 2009) suggesting that DRP3B promotes elonga-tion whereas DRP3A functions in constriction andscission Null drp5b alleles display larger and clusteredperoxisomes slight b-oxidation defects and growthdefects rescued by high CO2 (Zhang and Hu 2010)

PEX11s might recruit other fission machinery to theperoxisome once elongation has commenced All fiveArabidopsis PEX11 isoforms can bind FIS1A (Lingardet al 2008) and moss PEX11 and FIS1A interact at theperoxisomal membrane (Kamisugi et al 2016) More-over Arabidopsis DRP5B binds PEX11s as well asFIS1A DRP3A and DRP3B (Zhang and Hu 2010)

The plant-specific PEROXISOMAL AND MITO-CHONDRIAL DIVISION1 (PMD1) is a tail-anchoredmembrane protein that acts independently of PEX11sFIS1s and DRPs to promote peroxisome and mito-chondrial division (Aung and Hu 2011) pmd1mutantsdisplay elongated mitochondria and larger and fewerperoxisomes than wild type (Aung and Hu 2011) LikePEX11 (Mitsuya et al 2010) PMD1 promotes peroxi-some proliferation in response to salt (Frick and Strader2017) although this proliferation does not seem to impact

Figure 2 Peroxisome dynamics Peroxisome biogenesis and division are coordinated by peroxins (numbered ovals) that coor-dinate peroxisomalmembrane protein insertion into the ER or the peroxisomalmembrane After preperoxisomes bud from the ERperoxisomes mature through import of matrix proteins Peroxisomes can be degraded by pexophagy a type of specialized au-tophagy Dynamic peroxisome extensions (peroxules) assist peroxisome interactions with other organelles and can be associatedwith peroxisome division PEX11 promotes peroxisome division together with a group of proteins (PMD1 FIS1 DRP) that also actin division of mitochondria or chloroplasts PMP peroxisomal membrane protein


Kao et al


salt tolerance (Mitsuya et al 2010 Frick and Strader2017) Interestingly salt-induced proliferation alsorequires MAP Kinase 17 (Frick and Strader 2017)implying a role for phosphorylation in peroxisomeproliferation

MATRIX PROTEIN IMPORT CYCLING RECEPTORS

Cargo Selection by PTS1 and PTS2 Receptors

Matrix protein import (Fig 3) replenishes peroxi-somal contents and converts preperoxisomes to matureperoxisomes (Fig 2) Two types of peroxisome target-ing signals (PTS) specify matrix protein localizationMost matrix proteins carry a PTS1 a C-terminal SKLor similar tripeptide (Reumann 2004 Lingner et al2011) Fewer proteins carry the PTS2 nonapeptide oftenR[LI]X5HL in plants near the N terminus (Reumann2004) After delivery the PTS1 region is retainedwhereasthe approximately 30-amino acid N-terminal region ofplant PTS2 proteins is cleaved by the protease DEG15(Fig 3 Helm et al 2007 Schuhmann et al 2008) Al-though plants yeast and mammals use both PTS1 andPTS2 systems nematodes and fruit flies lack PTS2proteins (Gurvitz et al 2000 Motley et al 2000 Faustet al 2012)

Several algorithms predict plant PTS1 proteins in-cluding PredPlantPTS1 (Reumann et al 2012) andPPero (Wang et al 2017) Bioinformatic and proteomicapproaches have identified many potential peroxi-somal proteins in plants (for review see Reumann2011) These analyses have uncovered noncanonicalPTS1 signals and revealed the importance of residuesupstream of the PTS1 for targeting (Chowdhary et al2012) As not all predicted targeting signals conferperoxisomal localization (Ching et al 2012) fusions offluorescent reporters to candidate matrix proteins canbe used to visualize localization in transgenic plants(Mano et al 1999 Cassin-Ross and Hu 2014 Wu et al2016) or following transient transfection of tobaccoleaves (Reumann et al 2009 Quan et al 2013) cellculture (Mano et al 1999 Carrie et al 2007) or onionepidermal cells (Chowdhary et al 2012 Skouldinget al 2015)

PTS1 proteins are recognized by PEX5 (van der Leijet al 1993 Zolman et al 2000) and PTS2 proteins arerecognized by PEX7 (Fig 3 Marzioch et al 1994Braverman et al 1997 Woodward and Bartel 2005)Yeast PEX7 contains six WD40 domains forming aseven-bladed propeller that binds the PTS2 peptide onone face of PEX7 (Pan et al 2013) The C-terminal re-gion of PEX5 contains two clusters of tetratricopeptiderepeats that bind the PTS1 (Gatto et al 2000 Hagenet al 2015) The strength of in vitro binding of PTS1variants to PEX5 correlates with in vivo targeting effi-ciency in higher plants (Skoulding et al 2015) Peroxi-somal constituents alsomay affect import For examplenitric oxide donors and a calmodulin antagonist impairArabidopsis PTS1 import implicating nitric oxide andcalcium as import regulators (Corpas and Barroso2017)

Interestingly peroxisomes can import folded andoligomeric proteins (McNew and Goodman 1994 Leeet al 1997) which allows some endogenous proteinslacking a PTS to ldquopiggybackrdquo into peroxisomes (Katayaet al 2015) However the import machinery prefersmonomeric proteins (Freitas et al 2015) and PEX5binding to catalase (Freitas et al 2011) acyl-CoA oxi-dase1 and urate oxidase (Freitas et al 2015) preventsoligomerization of these cargo proteins

As in mammals (Braverman et al 1998 Otera et al1998) PEX7-PEX5 interactions allow PTS2 protein de-livery in plants (Hayashi et al 2005 Woodward andBartel 2005) In humans alternative splicing producestwo PEX5 forms a short form competent for PTS1 im-port and a long form facilitating both PTS1 and PTS2import (Dodt et al 1995 Braverman et al 1998) Al-though only one Arabidopsis PEX5 splice form isreported rice contains alternative forms and only thelong form binds PEX7 (Lee et al 2006) PEX5 and PEX7may interact via several regions The PEX5 N-terminalregion (1 to 230 amino acids) binds PEX7 in yeast two-hybrid assays (Nito et al 2002) and an Arabidopsispex5 variant lacking residues 314 to 334 fails to bindPEX7 in pull-down assays (Lanyon-Hogg et al 2014)The pex5-10 mutant and PEX5 RNAi lines display

Figure 3 Matrix protein import and receptor recycling Matrix proteinsharboring peroxisome-targeting signals are synthesized in the cytosolwhere they are recognized by the PEX5 (PTS1 proteins) or PEX7 (PTS2proteins) receptors Receptor-cargo complexes dock with PEX13-PEX14 which allows cargo release into the matrix Membrane-associatedPEX5 is ubiquitinated near the N-terminus by enzymes in the RINGcomplex assisted by the PEX4 ubiquitin-conjugating enzyme Mono-ubiquitinated or diubiquitinated PEX5 is recycled via removal from themembrane by the PEX1-PEX6 ATPase complex whereas PEX5 poly-ubiquitination can lead to PEX5 proteasomal degradation or may triggerpexophagy PTS2 proteins are processed in the matrix by the DEG15protease C C-terminus N N-terminus Ub ubiquitin




b-oxidation defects and impaired import of both PTS1and PTS2 proteins (Hayashi et al 2005 Zolman et al2005Khan andZolman 2010) Expressing anN-terminalPEX5 domain in pex5-10 restores PTS2 processingshowing that the PEX5 N-terminal domain promotesPEX7 function in vivo (Khan and Zolman 2010) More-over a special Arabidopsis pex5-1 (S318L) missense mu-tation confers inefficient b-oxidation and PTS2 import butnormal PTS1 import (Zolman et al 2000Woodward andBartel 2005)

Arabidopsis pex7 mutants display b-oxidation andPTS2 import defects (Hayashi et al 2005 Woodwardand Bartel 2005 Ramoacuten and Bartel 2010) Surprisinglyseveral pex7 mutations also impair PTS1 import andlower PEX5 levels (Ramoacuten and Bartel 2010) revealingthat PEX7 promotes PEX5 stability

In addition to targeting PEX5-PEX7 interactions mayinfluence cargo unloading Structural studies of Sac-charomyces cerevisiae peroxins reveal the PTS2 peptidesandwiched between PEX7 and its coreceptor PEX21(Pan et al 2013) which in yeast functions like plantPEX5 to bring PEX7 to the organelle Perhaps PEX5conformational changes during membrane insertion orPTS1 cargo unloading reconfigure PEX5-PTS2 cargo-PEX7 interactions to promote PTS2 cargo unloading

Docking Receptor-Cargo Complexes at the Peroxisome

The receptor-cargo complex docks with PEX13 andPEX14 on the peroxisomal membrane In yeast PEX5and PEX14 form a dynamic translocation pore with acargo-dependent diameter (Meinecke et al 2010)In plants the PEX14 N-terminal region binds PEX5WXXXFY domains (Nito et al 2002) in vitro labeltransfer assays implicate PEX14 as the first peroxisomalcontact of PEX5 during import (Bhogal et al 2016) andpex14mutants display impaired b-oxidation andmatrixprotein import (Hayashi et al 2000 Monroe-Augustuset al 2011 Burkhart et al 2013) However Arabi-dopsis pex14 null alleles are viable (Monroe-Augustuset al 2011) whereas pex13 null alleles confer lethality(Boisson-Dernier et al 2008) hinting that some yeastPEX14 roles might be provided by PEX13 in plantsPEX13 dysfunction results in expected physiologicaldefects a pex13 RNAi line and two missense pex13mutants aberrant peroxisome morphology 2 (apm2) andpex13-4 display b-oxidation and matrix protein importdefects (Mano et al 2006 Nito et al 2007 Woodwardet al 2014) Moreover the pex13-4 mutation lowersPEX5 membrane association and PEX5 overexpressionameliorates a subset of pex13-4 defects (Woodwardet al 2014) implying that the pex13-4 matrix proteinimport defects are due to impaired PEX5 docking

PEX13 binds PEX14 in yeast (Pires et al 2003) andmammals (Fransen et al 1998) but this interaction hasnot been reported in plants Yeast PEX13 interacts withPEX14 via a C-terminal Src homology 3 (SH3) domainand an intraperoxisomal sequence this interaction isessential for matrix protein import (Schell-Steven et al

2005) PEX13 also binds PEX5 and PEX7 in yeast(Douangamath et al 2002 Stein et al 2002 Pires et al2003) and mammals (Otera et al 2002) AlthoughArabidopsis PEX13 does bind to PEX7 (Mano et al2006) Arabidopsis PEX13 lacks a recognizable SH3domain (Boisson-Dernier et al 2008) and PEX5-PEX13interactions have not been reported in plants (Manoet al 2006) It remains to be determined if these ap-parent receptor docking differences reflect functionaldiversity or technical challenges

In addition to recruiting cargo-receptor complexes toperoxisomes docking complex-receptor interactions maypromote cargo unloading In Pichia pastoris PTS1 cargobinding enhances PEX5-PEX14 interaction but weakensPEX5-PEX13 interaction (Urquhart et al 2000) sug-gesting that PEX14 initiates docking and PEX13 promotesPTS1 cargo release Moreover the N-terminal regionof Arabidopsis PEX14 is sufficient to isolate PEX5 andPEX7 but not PTS2 cargo (Lanyon-Hogg et al 2014)suggesting that PEX14 bindingmight promote PTS2 cargounloading

Roles for Ubiquitination in Receptor Recycling andPeroxin Degradation

After cargo delivery ubiquitination promotes therecycling of cargo receptors from the peroxisomal mem-brane back to the cytosol (Fig 3) During ubiquitinationubiquitin-conjugating enzymes (UBCs) assist ubiquitin-protein ligases in covalently attaching ubiquitin tosubstrate proteins S cerevisiae PEX5 monoubiquitinationby the peroxisome-tethered UBC PEX4 and the peroxi-somal ubiquitin-protein ligase PEX12 (Platta et al 2009)allows a peroxisome-tetheredATPase complex to recyclePEX5 to the cytosol for further rounds of cargo recruit-ment (for review see Grimm et al 2012) In contrastPEX5 polyubiquitination by the cytosolic UBC4 actingwith the peroxisomal ubiquitin-protein ligase PEX2targets PEX5 for proteasomal degradation (Platta et al2009) The role of the third RING peroxin PEX10is controversialMammalian PEX10 is essential (Okumotoet al 2014) but yeast PEX10 only enhances PEX5ubiquitination (Platta et al 2009 El Magraoui et al2012)

Although PEX5 ubiquitination has not been directlydemonstrated in plants mutants defective in the peroxisome-associated ubiquitinationmachinery reveal roles in plantgrowth peroxisomal import andPEX5 retrotranslocationThe pex4-1 missense mutant and pex4 RNAi lines showimpairedb-oxidation andmatrix protein import (Zolmanet al 2005 Nito et al 2007) PEX5 accumulates (Kaoet al 2016) and is excessively membrane-associated(Ratzel et al 2011 Kao and Bartel 2015) in pex4-1 in-dicating that PEX4 promotes both PEX5 degradationand PEX5 retrotranslocation Moreover overexpressingPEX5 exacerbates pex4-1 defects (Kao and Bartel 2015)suggesting that PEX5 retention in the peroxisomalmembrane is detrimental Interestingly a T-DNA inser-tion upstream of the PEX13 start codon (pex13-1) that


Kao et al


lowers PEX13 transcripts alleviates pex4-1 growthdefects (Ratzel et al 2011) This suppression impliesthat decreasing receptor docking lessens the detrimentaleffects of PEX5 retention Similarly growth at ele-vated temperature lowers PEX5 levels and alleviatesthe peroxisomal defects in pex4 mutants (Kao andBartel 2015)PEX22 tethers PEX4 to the peroxisome (Fig 3) Arabi-

dopsis PEX22 was identified via its PEX4-binding abilityand can function in yeast when expressed together withArabidopsis PEX4 (Zolman et al 2005) Yeast PEX22enhances PEX4 enzymatic activity (El Magraoui et al2014) and a T-DNA insertion upstream of the Arabi-dopsis PEX22 start codon exacerbates the peroxisomaldefects of pex4-1 (Zolman et al 2005)The Arabidopsis PEX2 PEX10 and PEX12 RING per-

oxins all display in vitro ubiquitin-protein ligase activity(Kaur et al 2013) and are essential for embryogenesis (Huet al 2002 Schumann et al 2003 Sparkes et al 2003 Fanet al 2005 Prestele et al 2010) Expressing truncatedRING peroxins without the C-terminal catalytic zinc-binding RING domains (DZn) in wild type confersdominant-negative matrix protein import defects forPEX2-DZn and photorespiration defects attributed todecreased peroxisome-chloroplast interactions for PEX10-DZn (Prestele et al 2010) RNAi lines targeting RINGperoxin genes (Nito et al 2007) and several viable RINGperoxin mutants (Mano et al 2006 Burkhart et al 2014Kao et al 2016) show typical peroxisomal defects in-cluding impaired b-oxidation and matrix protein importMoreover PTS1 and PTS2 receptor levels are increased inRING peroxin mutants (Kao et al 2016) and PEX5 isexcessively membrane-associated in a pex12 mutant(Mano et al 2006) suggesting that the RING peroxinsfacilitate PEX5 and PEX7 retrotranslocationBoth Arabidopsis pex12 missense mutants are partial

loss-of-function alleles with Lys substitutions at adjacentamino acid residues (R170K in apm4 andE171K in pex12-1)in a relatively nonconserved 49 amino acid region lack-ing Lys residues (Mano et al 2006 Kao et al 2016)Surprisingly reducing PEX4 function ameliorates ratherthan exacerbates pex12-1 peroxisomal defects (Kao et al2016) This suppression suggests that the pex12-1 ectopicLys residue might provide an attachment site for PEX4-assisted ubiquitination triggering degradation of thepex12 proteinThe RING peroxins form a complex and each compo-

nent contributes to complex stability in yeast (Hazra et al2002 Agne et al 2003 Okumoto et al 2014) SimilarlyArabidopsis pex2-1 pex10-2 and pex12-1 mutants all dis-play decreased PEX10 levels (Kao et al 2016) Alongwithphysiological restoration pex4 mutants restore PEX10levels in pex12-1 (Kao et al 2016) Thus both PEX10 andPEX12 could be substrates along with PEX5 of the per-oxisomal ubiquitination machineryThe RING peroxins may not be the only peroxisome-

associated ubiquitin-protein ligases The suppressorof plastid protein import locus 1 (SP1) is a RING-typeubiquitin-protein ligase localizing on chloroplastswhere it promotes degradation of several outer envelope

translocon components (Ling et al 2012) andmodulatesabiotic stress tolerance (Ling and Jarvis 2015) A recentreport suggests that SP1 also can localize to peroxisomesand interact with the docking peroxins where it pro-motes PEX13 ubiquitination and degradation (Pan et al2016) Loss of SP1 increases b-oxidation in wild type andimproves peroxisome function in pex13-1 and pex14-2mutants (Pan et al 2016) Interestingly sp1 mutantsexacerbate pex4-1 defects (Pan et al 2016) consistentwith the hypothesis that excessive docking capacity isdetrimental when PEX5 recycling is impaired (Ratzelet al 2011) However SP1 peroxisomal localization maydepend on overexpression and PEX13 and PEX14 levelsdo not consistently vary with SP1 accumulation inseedlings (Ling et al 2017) highlighting the possibilitythat peroxisome-related sp1 phenotypes may be indirecteffects of altered chloroplast function

Like SP1 PEX2 may impact both chloroplasts andperoxisomes A pex2 missense allele (ted3) suppressesthe photomorphogenic defects of the de-etiolated1 (det1)mutant (Hu et al 2002) and expressing a GFP-fusedPEX2 RING domain slightly ameliorates det1 growthdefects (Desai et al 2014) Many metabolic pathwaysare shared among organelles For example photores-piration requires enzymes acting in peroxisomeschloroplasts and mitochondria suggesting that addi-tional shared regulatory machinery awaits discovery

Recycling of the PTS2 receptor PEX7 is not well un-derstood In mammals PEX7 export requires PEX5export (Rodrigues et al 2014) and dysfunctional PEX7is ubiquitinated and degraded (Miyauchi-Nanri et al2014) Disrupting PEX5 recycling increases PEX7 levelsin P pastoris (Hagstrom et al 2014) and Arabidopsis(Kao et al 2016) suggesting coordinated degradationIn addition two Arabidopsis Rab GTPases bind GFP-PEX7 on the peroxisomal membrane and promote pro-teasomal degradation ofmembrane-associated PEX7 (Cuiet al 2013) Whether these Rab GTPases impact PEX5recycling or the peroxisomal ubiquitination machinery isunknown

ATP-Dependent Receptor Retrotranslocation

Monoubiquitinated PEX5 is returned to the cytosolby a peroxisome-tethered ATPase complex (Fig 3)PEX1 and PEX6 are members of the ATPases associatedwith diverse cellular activities family and function inyeast as a trimer of PEX1-PEX6 dimers (Blok et al 2015Ciniawsky et al 2015 Gardner et al 2015) The PEX1-PEX6 heterohexamer is tethered to the peroxisomeby a tail-anchored protein known as PEX15 in yeast(Elgersma et al 1997) PEX26 in mammals (Matsumotoet al 2003) and APEM9DAYUPEX26 in plants (Gotoet al 2011 Li et al 2014 Gonzalez et al 2017) PEX26binds PEX1-PEX6 via PEX6 (Birschmann et al 2003Matsumoto et al 2003 Goto et al 2011) Unlike PEX22enhancement of PEX4 activity (El Magraoui et al 2014)tether binding decreases PEX1-PEX6 ATPase activityin yeast (Gardner et al 2015) In addition to tethering




PEX1-PEX6 mammalian PEX26 interacts with the PEX14docking peroxin (Tamura et al 2014) hinting that PEX26may bridge the import and export machinery

Arabidopsis RNAi lines targeting PEX1 PEX6 orPEX26 display decreased b-oxidation and matrix pro-tein import (Nito et al 2007 Goto et al 2011) Al-though PEX1 is the most commonly mutated gene inperoxisome biogenesis disorder patients (for reviewsee Braverman et al 2016) Arabidopsis pex1 mutantswere only recently reported (Rinaldi et al 2017) pex1-3is inviable when homozygous and displays impairedmatrix protein import and enlarged peroxisomes whenheterozygous (Rinaldi et al 2017) pex1-2 displays im-paired matrix protein import and low levels of bothPEX1 and PEX6 (Rinaldi et al 2017) suggesting thatPEX1 normally stabilizes PEX6 Overexpressing PEX6restores PEX1 levels and ameliorates pex1-2 peroxi-somal defects (Rinaldi et al 2017) suggesting recipro-cal stabilization of PEX1 by PEX6

Four Arabidopsis pex6 mutants have been charac-terized pex6-1 pex6-3 and pex6-4 alter residues near thesecond ATPase domain (Zolman and Bartel 2004Gonzalez et al 2017) and display decreasedb-oxidationdelayed oil body utilization impaired matrix proteinimport low PEX5 levels (Zolman and Bartel 2004Gonzalez et al 2017) and increased PEX5 membraneassociation (Ratzel et al 2011 Gonzalez et al 2017)implying that PEX5 is degraded when recycling is im-paired (Fig 3) The atypical pex6-2 mutant displayselevated PEX5 levels and delayed matrix protein deg-radation but resembles wild type in most measures ofperoxisome function (Burkhart et al 2013 Gonzalezet al 2017)

Arabidopsis pex26 null mutants display embryo le-thality (Goto et al 2011) and pollen maturation defects(Li et al 2014) The viable aberrant peroxisome morphol-ogy9 missense allele shows wild-type b-oxidation butimpaired matrix protein import in some cells (Gotoet al 2011) The pex26-1 splice-site mutation confersb-oxidation deficiency and low PEX5 levels like typicalpex6 mutants (Gonzalez et al 2017) Mutations in PEX4or RINGperoxins restore PEX5 levels in pex26-1 (Gonzalezet al 2017) and a pex4mutant restores PEX5 levels inpex6-1 (Ratzel et al 2011) suggesting that ubiquiti-nation triggers the heightened PEX5 degradationobserved in these mutants Together the evidencesuggests that ubiquitination drives PEX5 recycling ordegradation in plants as in other eukaryotes (Fig 3)but direct demonstration of PEX5 ubiquitination inplants would bolster this conclusion

Overexpressing PEX5 worsens the peroxisomal de-fects of pex1-2 (Rinaldi et al 2017) pex4-1 (Kao andBartel 2015) pex6-2 (Burkhart et al 2013) pex6-4(Gonzalez et al 2017) and pex26-1 (Gonzalez et al2017) suggesting that PEX5 impedes peroxisome func-tion when not efficiently recycled In contrast over-expressing PEX5 ameliorates pex6-1 (Zolman and Bartel2004) and pex6-3 (Gonzalez et al 2017) defects Thesedifferences hint that the PEX1-PEX6 complex may retro-translocate not onlymonoubiquitinatedPEX5 for recycling

but perhaps also polyubiquitinated substrates for pro-teasomal degradation (Gonzalez et al 2017)

QUALITY CONTROL AND PEXOPHAGY

Peroxisomes house many oxidative reactions (Fig 1)and although antioxidative enzymes can detoxify ROSperoxisomes and their constituents are still likely to bedamaged and require turnover Eukaryotes dispose oflarge cytosolic components including organelles viaautophagy (for review see Li and Vierstra 2012) Per-oxisome turnover is mediated by selective autophagyof peroxisomes or pexophagy (for review see Youngand Bartel 2016)

Various organisms use different signals to recruit au-tophagy receptors during pexophagy (for review seeHonsho et al 2016) complicating the search forpexophagy-specific machinery in Arabidopsis In Han-senula polymorpha PEX14 is the only peroxin requiredfor pexophagy (Zutphen et al 2008) In S cerevisiae PEX3recruits a yeast-specific autophagy-relatedproteinATG36to target the organelle for degradation (Motley et al 2012)In mammals Neighbor of BRCA1 Gene 1 and p62 triggerpexophagy by linking the autophagy machinery to ubiq-uitinated proteins on the peroxisome surface (Deosaranet al 2013) expressing a cytosol-facing ubiquitin-taggedPMP is sufficient to trigger pexophagy (Kim et al 2008)PEX2-mediated ubiquitination of PEX5 or PMP70 triggerspexophagy during starvation (Sargent et al 2016) andROS increase PEX5 phosphorylation leading to PEX5ubiquitination and subsequent p62-mediated pexophagy(Zhang et al 2015)

Arabidopsis pexophagy was recently demonstrated(Farmer et al 2013 Kim et al 2013 Shibata et al 2013)During seedling development peroxisome functions shiftfrom fatty acid utilization to photorespiration (Titus andBecker 1985 Nishimura et al 1986 Sautter 1986 Lingardet al 2009) Autophagy mutants accumulate peroxisomalproteins (Shibata et al 2013 Yoshimoto et al 2014) andperoxisomes (Kim et al 2013 Yoshimoto et al 2014)during this transition suggesting a role for pexophagy inclearing obsolete peroxisomes Moreover autophagy-defective mutants were recovered in a microscopy-basedscreen for aggregated peroxisomes (Shibata et al 2013)H2O2 treatment or reducing catalase function also results inperoxisome clustering in autophagy-defective mutants(Shibata et al 2013 Yoshimoto et al 2014) These findingssuggest that oxidatively damaged peroxisomes are de-graded via autophagy

The autophagy machinery coordinates peroxisomeabundance together with the peroxisomal matrix pro-tease LON2 (Farmer et al 2013) The chaperone activityof LON2 normally inhibits pexophagy (Goto-Yamadaet al 2014) and as cells age lon2 mutants developb-oxidation defects and low peroxisomal protein levels(Lingard and Bartel 2009) due to heightened pexophagy(Farmer et al 2013)

Interestingly lon2 and PEX1pex1-3 peroxisomesappear enlarged and preventing autophagy restores


Kao et al


peroxisome size in both mutants (Farmer et al 2013Goto-Yamada et al 2014 Rinaldi et al 2017) sug-gesting that these enlarged peroxisomes are pexophagyintermediates PEX1 dysfunction in yeast (Nuttall et al2014) and mammalian cells (Law et al 2017) also trig-gers pexophagy These findings imply that LON2 andor PEX1-PEX6 clients perhaps including ubiquitinatedPEX5 promote pexophagy in plantsAutophagy receptors often bind the ubiquitin-like

protein ATG8 which decorates the growing autophago-some membrane (for review see Li and Vierstra 2012)Intriguingly the Arabidopsis RING peroxin PEX10 andthe ATPase PEX6 bind ATG8 in bimolecular fluorescencecomplementation assays (Xie et al 2016) MoreoverArabidopsis DSK2 a ubiquitin-binding protein that in-teracts with the RING domains of PEX2 and PEX12 (Kauret al 2013) also binds ATG8 and promotes selectiveautophagy of a growth-promoting transcription factor(Nolan et al 2017) Characterizing pexophagy in pex ordsk2 mutants might assist in identifying the moleculartriggers and receptors for pexophagy in plants

FUTURE PERSPECTIVES

Although our understanding of plant peroxisomebiology is expanding much remains to be discovered(see Outstanding Questions) The enzymes catalyzingperoxisomal fatty acid metabolism photorespirationand ROS inactivation are identified but how matrixprotein levels are controlled how metabolites leave theorganelle how peroxisomes function as both sourcesand sinks of ROS and RNS and how peroxisome-derived ROS and RNS integrate with signals fromother organelles remain mysteriousHow peroxisome biogenesis from the ER is balanced

with division of existing organelles is an open questionIn addition to our limited understanding of peroxisomebiogenesis from the ER the proteins implicated in plantperoxisome division are redundantly encoded in plantsand often also participate in division of mitochondria orchloroplasts making it challenging to isolate the rolesof peroxisome division in plant physiology Moreoveralthough the peroxins that directly mediate peroxisomebiogenesis and division are identified the transcrip-tional regulation of plant PEX genes is understudiedand only a few factors involved in PEX11 expressionare identified (Desai and Hu 2008 Desai et al 2017)Although peroxins were initially discovered due to

their roles in peroxisome biogenesis additional func-tions for these proteins continue to emerge The peroxinsthat mediate PEX5 ubiquitination and retrotranslocation(Fig 3) resemble enzymes acting in ER-associated deg-radation (for review see Schliebs et al 2010) and evi-dence is mounting that these receptor-recycling peroxinsmay ubiquitinate and remove additional clients from theperoxisomal membrane (Burkhart et al 2014 Kao et al2016 Gonzalez et al 2017) Mammalian PEX3 andPEX19 function not only in PMP insertion but also ininserting the lipid droplet- and ER-associated hairpin

protein UBXD8 (Schrul and Kopito 2016) Moreovermammalian PEX3 and PEX13 promote autophagy ofmitochondria (mitophagy) whereas PEX19 and PEX14are necessary for general autophagy (Lee et al 2017)The dual roles of peroxins acting in biogenesis and toattract autophagy machinery (Zutphen et al 2008Motley et al 2012 Xie et al 2016) hint at mechanisms totrigger peroxisome degradation when import becomesdysfunctional These discoveries highlight the intimaterelationships among organelles and prompt the questionof whether plant peroxins are similarly promiscuous

Given the close metabolic connections between per-oxisomes and other organelles it is not surprising thattight physical associations are observed for exampleamong peroxisomes and the ER (Barton et al 2013) andchloroplasts (Schumann et al 2007 Oikawa et al2015) Peroxules can mediate interorganellar contactssuch as among peroxisomes and ER (Sinclair et al2009) oil bodies (Thazar-Poulot et al 2015) mito-chondria (Jaipargas et al 2016) and chloroplasts (Gaoet al 2016) Moreover peroxules can respond to envi-ronmental signals For example peroxules are inducedby oxidative stress (Sinclair et al 2009) and high lightrapidly induces peroxule interactions with mitochon-dria (Jaipargas et al 2016) The study of peroxule dy-namics is in its infancy and how proteins on theperoxisome and target organelle mediate these inter-actions awaits discovery




Finally much of what we know about plant peroxi-some biogenesis and function comes from researchusing the reference plant Arabidopsis Additional ge-netic investigations in other plants including in non-oilseed crop plants (Mendiondo et al 2014) andnonflowering plants (Kamisugi et al 2016) are neededto understand the diverse roles and regulation of per-oxisomes throughout the plant kingdom New chemicaltools to visualize (Landrum et al 2010 Fahy et al 2017)and disrupt (Brown et al 2011 2013) plant peroxisomeswill likely accelerate these studies

ACKNOWLEDGMENTS

We apologize to those whose work could not be discussed due to lengthconstraints We are grateful to Kathryn Hamilton Roxanna Llinas AndrewWoodward Zachary Wright Pierce Young and two anonymous reviewers forcritical comments on the manuscript

Received July 28 2017 accepted October 9 2017 published October 11 2017

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Agrawal G Fassas SN Xia ZJ Subramani S (2016) Distinct requirementsfor intra-ER sorting and budding of peroxisomal membrane proteinsfrom the ER J Cell Biol 212 335ndash348

Aung K Hu J (2011) The Arabidopsis tail-anchored protein PEROXISOMALAND MITOCHONDRIAL DIVISION FACTOR1 is involved in the morpho-genesis and proliferation of peroxisomes and mitochondria Plant Cell 234446ndash4461

Bartel B Burkhart SE Fleming WA (2014) Protein transport in and out ofplant peroxisomes In C Brocard A Hartig eds Molecular MachinesInvolved in Peroxisome Biogenesis and Maintenance Springer ViennaAustria pp 325-345

Barton K Mathur N Mathur J (2013) Simultaneous live-imaging of per-oxisomes and the ER in plant cells suggests contiguity but no luminalcontinuity between the two organelles Front Physiol 4 196

Bauwe H Hagemann M Fernie AR (2010) Photorespiration playerspartners and origin Trends Plant Sci 15 330ndash336

Bernhardt K Wilkinson S Weber AP Linka N (2012) A peroxisomalcarrier delivers NAD+ and contributes to optimal fatty acid degradationduring storage oil mobilization Plant J 69 1ndash13

Bhogal MS Lanyon-Hogg T Johnston KA Warriner SL Baker A (2016)Covalent label transfer between peroxisomal importomer componentsreveals export-driven import interactions J Biol Chem 291 2460ndash2468

Birschmann I Stroobants AK van den Berg M Schaumlfer A Rosenkranz KKunau WH Tabak HF (2003) Pex15p of Saccharomyces cerevisiae pro-vides a molecular basis for recruitment of the AAA peroxin Pex6p toperoxisomal membranes Mol Biol Cell 14 2226ndash2236

Blok NB Tan D Wang RY Penczek PA Baker D DiMaio F RapoportTA Walz T (2015) Unique double-ring structure of the peroxisomalPex1Pex6 ATPase complex revealed by cryo-electron microscopy ProcNatl Acad Sci USA 112 E4017ndashE4025

Boisson-Dernier A Frietsch S Kim TH Dizon MB Schroeder JI (2008)The peroxin loss-of-function mutation abstinence by mutual consent dis-rupts male-female gametophyte recognition Curr Biol 18 63ndash68

Braverman N Dodt G Gould SJ Valle D (1998) An isoform of pex5p thehuman PTS1 receptor is required for the import of PTS2 proteins intoperoxisomes Hum Mol Genet 7 1195ndash1205

Braverman N Steel G Obie C Moser A Moser H Gould SJ Valle D(1997) Human PEX7 encodes the peroxisomal PTS2 receptor and is re-sponsible for rhizomelic chondrodysplasia punctata Nat Genet 15 369ndash376

Braverman NE Raymond GV Rizzo WB Moser AB Wilkinson MEStone EM Steinberg SJ Wangler MF Rush ET Hacia JG Bose M(2016) Peroxisome biogenesis disorders in the Zellweger spectrum an

overview of current diagnosis clinical manifestations and treatmentguidelines Mol Genet Metab 117 313ndash321

Brown LA Larson TR Graham IA Hawes C Paudyal R Warriner SLBaker A (2013) An inhibitor of oil body mobilization in Arabidopsis NewPhytol 200 641ndash649

Brown LA OrsquoLeary-Steele C Brookes P Armitage L Kepinski SWarriner SL Baker A (2011) A small molecule with differential effectson the PTS1 and PTS2 peroxisome matrix import pathways Plant J 65980ndash990

Burkhart SE Kao YT Bartel B (2014) Peroxisomal ubiquitin-protein ligasesperoxin2 and peroxin10 have distinct but synergistic roles in matrixprotein import and peroxin5 retrotranslocation in Arabidopsis PlantPhysiol 166 1329ndash1344

Burkhart SE Lingard MJ Bartel B (2013) Genetic dissection of peroxisome-associated matrix protein degradation in Arabidopsis thaliana Genetics193 125ndash141

Bussell JD Reichelt M Wiszniewski AA Gershenzon J Smith SM (2014)Peroxisomal ATP-binding cassette transporter COMATOSE and themultifunctional protein abnormal INFLORESCENCE MERISTEM arerequired for the production of benzoylated metabolites in Arabidopsisseeds Plant Physiol 164 48ndash54

Carrie C Murcha MW Millar AH Smith SM Whelan J (2007) Nine3-ketoacyl-CoA thiolases (KATs) and acetoacetyl-CoA thiolases (ACATs) en-coded by five genes inArabidopsis thaliana are targeted either to peroxisomes orcytosol but not to mitochondria Plant Mol Biol 63 97ndash108

Cassin-Ross G Hu J (2014) Systematic phenotypic screen of Arabidopsisperoxisomal mutants identifies proteins involved in b-oxidation PlantPhysiol 166 1546ndash1559

Chapman KD Trelease RN (1991) Acquisition of membrane lipids bydifferentiating glyoxysomes role of lipid bodies J Cell Biol 115 995ndash1007

Charlton WL Johnson B Graham IA Baker A (2005) Non-coordinateexpression of peroxisome biogenesis b-oxidation and glyoxylate cyclegenes in mature Arabidopsis plants Plant Cell Rep 23 647ndash653

Chen Y Pieuchot L Loh RA Yang J Kari TM Wong JY Jedd G (2014)Hydrophobic handoff for direct delivery of peroxisome tail-anchoredproteins Nat Commun 5 5790

Ching SL Gidda SK Rochon A van Cauwenberghe OR Shelp BJMullen RT (2012) Glyoxylate reductase isoform 1 is localized in thecytosol and not peroxisomes in plant cells J Integr Plant Biol 54 152ndash168

Chowdhary G Kataya AR Lingner T Reumann S (2012) Non-canonicalperoxisome targeting signals identification of novel PTS1 tripeptidesand characterization of enhancer elements by computational permuta-tion analysis BMC Plant Biol 12 142

Ciniawsky S Grimm I Saffian D Girzalsky W Erdmann R Wendler P(2015) Molecular snapshots of the Pex16 AAA+ complex in action NatCommun 6 7331

Contento AL Bassham DC (2010) Increase in catalase-3 activity as a re-sponse to use of alternative catabolic substrates during sucrose starva-tion Plant Physiol Biochem 48 232ndash238

Corpas FJ Barroso JB (2017) Calmodulin antagonist affects peroxisomalfunctionality by disrupting both peroxisomal Ca2+ and protein import JCell Sci Feb 9 pii jcs201467 doi 101242jcs201467 [Epub ahead ofprint]

Corpas FJ Barroso JB Palma JM Rodriguez-Ruiz M (2017) Plant perox-isomes a nitro-oxidative cocktail Redox Biol 11 535ndash542

Cruz Castillo M Martiacutenez C Buchala A Meacutetraux JP Leoacuten J (2004) Gene-specific involvement of beta-oxidation in wound-activated responses inArabidopsis Plant Physiol 135 85ndash94

Cui S Fukao Y Mano S Yamada K Hayashi M Nishimura M (2013)Proteomic analysis reveals that the Rab GTPase RabE1c is involved inthe degradation of the peroxisomal protein receptor PEX7 (peroxin 7) JBiol Chem 288 6014ndash6023

Cui S Hayashi Y Otomo M Mano S Oikawa K Hayashi M NishimuraM (2016) Sucrose production mediated by lipid metabolism suppressesthe physical interaction of peroxisomes and oil bodies during germi-nation of Arabidopsis thaliana J Biol Chem 291 19734ndash19745

De Marcos Lousa C van Roermund CW Postis VL Dietrich D Kerr IDWanders RJ Baldwin SA Baker A Theodoulou FL (2013) Intrinsicacyl-CoA thioesterase activity of a peroxisomal ATP binding cassettetransporter is required for transport and metabolism of fatty acids ProcNatl Acad Sci USA 110 1279ndash1284


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De Rybel B Audenaert D Xuan W Overvoorde P Strader LC KepinskiS Hoye R Brisbois R Parizot B Vanneste S Liu X Gilday A et al(2012) A role for the root cap in root branching revealed by the non-auxin probe naxillin Nat Chem Biol 8 798ndash805

Del Riacuteo LA Loacutepez-Huertas E (2016) ROS generation in peroxisomes and itsrole in cell signaling Plant Cell Physiol 57 1364ndash1376

Delker C Zolman BK Miersch O Wasternack C (2007) Jasmonate bio-synthesis in Arabidopsis thaliana requires peroxisomal b-oxidation enzymesmdashadditional proof by properties of pex6 and aim1 Phytochemistry 68 1642ndash1650

Dellero Y Jossier M Glab N Oury C Tcherkez G Hodges M (2016)Decreased glycolate oxidase activity leads to altered carbon allocationand leaf senescence after a transfer from high CO2 to ambient air inArabidopsis thaliana J Exp Bot 67 3149ndash3163

Dempsey DA Klessig DF (2017) How does the multifaceted plant hor-mone salicylic acid combat disease in plants and are similar mechanismsutilized in humans BMC Biol 15 23

Deosaran E Larsen KB Hua R Sargent G Wang Y Kim S Lamark TJauregui M Law K Lippincott-Schwartz J Brech A Johansen T et al(2013) NBR1 acts as an autophagy receptor for peroxisomes J Cell Sci126 939ndash952

Desai M Hu J (2008) Light induces peroxisome proliferation in Arabidopsisseedlings through the photoreceptor phytochrome A the transcriptionfactor HY5 HOMOLOG and the peroxisomal protein PEROXIN11bPlant Physiol 146 1117ndash1127

Desai M Kaur N Hu J (2014) Ectopic expression of the RING domain ofthe Arabidopsis peroxin2 protein partially suppresses the phenotype ofthe photomorphogenic mutant de-etiolated1 PLoS One 9 e108473

Desai M Pan R Hu J (2017) Arabidopsis Forkhead-Associated DomainProtein 3 negatively regulates peroxisome division J Integr Plant Biol59 454ndash458

Dodt G Braverman N Wong C Moser A Moser HW Watkins P Valle DGould SJ (1995) Mutations in the PTS1 receptor gene PXR1 definecomplementation group 2 of the peroxisome biogenesis disorders NatGenet 9 115ndash125

Dong CH Zolman BK Bartel B Lee BH Stevenson B Agarwal M ZhuJK (2009) Disruption of Arabidopsis CHY1 reveals an important role ofmetabolic status in plant cold stress signaling Mol Plant 2 59ndash72

Douangamath A Filipp FV Klein AT Barnett P Zou P Voorn-BrouwerT Vega MC Mayans OM Sattler M Distel B Wilmanns M (2002)Topography for independent binding of a-helical and PPII-helical lig-ands to a peroxisomal SH3 domain Mol Cell 10 1007ndash1017

Eastmond PJ (2007) MONODEHYROASCORBATE REDUCTASE4 is re-quired for seed storage oil hydrolysis and postgerminative growth inArabidopsis Plant Cell 19 1376ndash1387

Eastmond PJ (2006) SUGAR-DEPENDENT1 encodes a patatin domain tri-acylglycerol lipase that initiates storage oil breakdown in germinatingArabidopsis seeds Plant Cell 18 665ndash675

El Magraoui F Baumlumer BE Platta HW Baumann JS GirzalskyW Erdmann R(2012) The RING-type ubiquitin ligases Pex2p Pex10p and Pex12p form aheteromeric complex that displays enhanced activity in an ubiquitin conju-gating enzyme-selective manner FEBS J 279 2060ndash2070

El Magraoui F Schroumltter A Brinkmeier R Kunst L Mastalski T MuumlllerT Marcus K Meyer HE Girzalsky W Erdmann R Platta HW (2014)The cytosolic domain of Pex22p stimulates the Pex4p-dependent ubiq-uitination of the PTS1-receptor PLoS One 9 e105894

Elgersma Y Kwast L van den Berg M Snyder WB Distel B SubramaniS Tabak HF (1997) Overexpression of Pex15p a phosphorylated per-oxisomal integral membrane protein required for peroxisome assemblyin S cerevisiae causes proliferation of the endoplasmic reticulum membraneEMBO J 16 7326ndash7341

Fahy D Sanad MN Duscha K Lyons M Liu F Bozhkov P Kunz HH HuJ Neuhaus HE Steel PG Smertenko A (2017) Impact of salt stress celldeath and autophagy on peroxisomes quantitative and morphologicalanalyses using small fluorescent probe N-BODIPY Sci Rep 7 39069

Fan J Quan S Orth T Awai C Chory J Hu J (2005) The Arabidopsis PEX12gene is required for peroxisome biogenesis and is essential for devel-opment Plant Physiol 139 231ndash239

Fan J Yu L Xu C (2017) A central role for triacylglycerol in membrane lipidbreakdown fatty acid b-oxidation and plant survival under extendeddarkness Plant Physiol 174 1517ndash1530

Farmer LM Rinaldi MA Young PG Danan CH Burkhart SE Bartel B(2013) Disrupting autophagy restores peroxisome function to an Arabidopsis

lon2 mutant and reveals a role for the LON2 protease in peroxisomal matrixprotein degradation Plant Cell 25 4085ndash4100

Faust JE Verma A Peng C McNew JA (2012) An inventory of peroxisomalproteins and pathways in Drosophila melanogaster Traffic 13 1378ndash1392

Footitt S Slocombe SP Larner V Kurup S Wu Y Larson T Graham IBaker A Holdsworth M (2002) Control of germination and lipid mo-bilization by COMATOSE the Arabidopsis homologue of human ALDPEMBO J 21 2912ndash2922

Fransen M Terlecky SR Subramani S (1998) Identification of a humanPTS1 receptor docking protein directly required for peroxisomal proteinimport Proc Natl Acad Sci USA 95 8087ndash8092

Freitas MO Francisco T Rodrigues TA Alencastre IS Pinto MP Grou CPCarvalho AF Fransen M Saacute-Miranda C Azevedo JE (2011) PEX5 proteinbinds monomeric catalase blocking its tetramerization and releases it uponbinding the N-terminal domain of PEX14 J Biol Chem 286 40509ndash40519

Freitas MO Francisco T Rodrigues TA Lismont C Domingues P PintoMP Grou CP Fransen M Azevedo JE (2015) The peroxisomal proteinimport machinery displays a preference for monomeric substrates OpenBiol 5 140236

Frick EM Strader LC (2017) Kinase MPK17 and the peroxisome divisionfactor PMD1 influence salt-induced peroxisome proliferation PlantPhysiol Sep 20 pii pp010192017 doi 101104pp1701019 [Epubahead of print]

Fujimoto M Arimura S Mano S Kondo M Saito C Ueda T NakazonoM Nakano A Nishimura M Tsutsumi N (2009) Arabidopsis dynamin-related proteins DRP3A and DRP3B are functionally redundant in mi-tochondrial fission but have distinct roles in peroxisomal fission Plant J58 388ndash400

Fulda M Schnurr J Abbadi A Heinz E Browse J (2004) Peroxisomal Acyl-CoA synthetase activity is essential for seedling development in Arabi-dopsis thaliana Plant Cell 16 394ndash405

Gao H Metz J Teanby NA Ward AD Botchway SW Coles B PollardMR Sparkes I (2016) In vivo quantification of peroxisome tethering tochloroplasts in tobacco epidermal cells using optical tweezers PlantPhysiol 170 263ndash272

Gardner BM Chowdhury S Lander GC Martin A (2015) The Pex1Pex6complex is a heterohexameric AAA+ motor with alternating and highlycoordinated subunits J Mol Biol 427(6 Pt B) 1375ndash1388

Gatto GJ Jr Geisbrecht BV Gould SJ Berg JM (2000) Peroxisomal tar-geting signal-1 recognition by the TPR domains of human PEX5 NatStruct Biol 7 1091ndash1095

Germain V Rylott EL Larson TR Sherson SM Bechtold N Carde JPBryce JH Graham IA Smith SM (2001) Requirement for 3-ketoacyl-CoA thiolase-2 in peroxisome development fatty acid b-oxidation andbreakdown of triacylglycerol in lipid bodies of Arabidopsis seedlingsPlant J 28 1ndash12

Gonzalez KL Fleming WA Kao YT Wright ZJ Venkova SV VenturaMJ Bartel B (2017) Disparate peroxisome-related defects in Arabidopsispex6 and pex26 mutants link peroxisomal retrotranslocation and oil bodyutilization Plant J 92 110ndash128

Goto S Mano S Nakamori C Nishimura M (2011) Arabidopsis ABERRANTPEROXISOME MORPHOLOGY9 is a peroxin that recruits the PEX1-PEX6complex to peroxisomes Plant Cell 23 1573ndash1587

Goto-Yamada S Mano S Nakamori C Kondo M Yamawaki R Kato ANishimura M (2014) Chaperone and protease functions of LON protease2 modulate the peroxisomal transition and degradation with autophagyPlant Cell Physiol 55 482ndash496

Goto-Yamada SMano S Yamada K OikawaK Hosokawa Y Hara-Nishimura INishimura M (2015) Dynamics of the light-dependent transition of plantperoxisomes Plant Cell Physiol 56 1264ndash1271

Graham IA (2008) Seed storage oil mobilization Annu Rev Plant Biol 59115ndash142

Grimm I Saffian D Platta HW Erdmann R (2012) The AAA-type ATPasesPex1p and Pex6p and their role in peroxisomal matrix protein import inSaccharomyces cerevisiae Biochim Biophys Acta 1823 150ndash158

Gurvitz A Langer S Piskacek M Hamilton B Ruis H Hartig A (2000)Predicting the function and subcellular location of Caenorhabditis elegansproteins similar to Saccharomyces cerevisiae b-oxidation enzymes Yeast17 188ndash200

Hagen S Drepper F Fischer S Fodor K Passon D Platta HW Zenn MSchliebs W Girzalsky W Wilmanns M Warscheid B Erdmann R(2015) Structural insights into cargo recognition by the yeast PTS1 re-ceptor J Biol Chem 290 26610ndash26626




Hagstrom D Ma C Guha-Polley S Subramani S (2014) The unique deg-radation pathway of the PTS2 receptor Pex7 is dependent on the PTSreceptorcoreceptor Pex5 and Pex20 Mol Biol Cell 25 2634ndash2643

Hayashi M Nito K Takei-Hoshi R Yagi M KondoM Suenaga A Yamaya TNishimuraM (2002) Ped3p is a peroxisomal ATP-binding cassette transporterthat might supply substrates for fatty acid b-oxidation Plant Cell Physiol 431ndash11

Hayashi M Nito K Toriyama-Kato K Kondo M Yamaya T Nishimura M(2000) AtPex14p maintains peroxisomal functions by determining pro-tein targeting to three kinds of plant peroxisomes EMBO J 19 5701ndash5710

Hayashi M Yagi M Nito K Kamada T Nishimura M (2005) Differentialcontribution of two peroxisomal protein receptors to the maintenance ofperoxisomal functions in Arabidopsis J Biol Chem 280 14829ndash14835

Hayashi Y Hayashi M Hayashi H Hara-Nishimura I Nishimura M(2001) Direct interaction between glyoxysomes and lipid bodies in cot-yledons of the Arabidopsis thaliana ped1 mutant Protoplasma 218 83ndash94

Hayward AP Moreno MA Howard III TP Hague J Nelson K Heffel-finger C Romero S Kausch AP Glauser G Acosta IF Mottinger JPDellaporta SL (2016) Control of sexuality by the sk1-encoded UDP-glycosyltransferase of maize Sci Adv 2 e1600991

Hazra PP Suriapranata I Snyder WB Subramani S (2002) Peroxisomeremnants in pex3D cells and the requirement of Pex3p for interactionsbetween the peroxisomal docking and translocation subcomplexesTraffic 3 560ndash574

Helm M Luumlck C Prestele J Hierl G Huesgen PF Froumlhlich T Arnold GJAdamska I Goumlrg A Lottspeich F Gietl C (2007) Dual specificities of theglyoxysomalperoxisomal processing protease Deg15 in higher plantsProc Natl Acad Sci USA 104 11501ndash11506

Hetherington AM Woodward FI (2003) The role of stomata in sensing anddriving environmental change Nature 424 901ndash908

Honsho M Yamashita S Fujiki Y (2016) Peroxisome homeostasis mech-anisms of division and selective degradation of peroxisomes in mam-mals Biochim Biophys Acta 1863 984ndash991

Hu J Aguirre M Peto C Alonso J Ecker J Chory J (2002) A role forperoxisomes in photomorphogenesis and development of ArabidopsisScience 297 405ndash409

Hu J Baker A Bartel B Linka N Mullen RT Reumann S Zolman BK (2012)Plant peroxisomes biogenesis and function Plant Cell 24 2279ndash2303

Hua R Gidda SK Aranovich A Mullen RT Kim PK (2015) Multipledomains in PEX16 mediate its trafficking and recruitment of peroxi-somal proteins to the ER Traffic 16 832ndash852

Jaipargas EA Mathur N Bou Daher F Wasteneys GO Mathur J (2016)High light intensity leads to increased peroxule-mitochondria interac-tions in plants Front Cell Dev Biol 4 6

James CN Horn PJ Case CR Gidda SK Zhang D Mullen RT Dyer JMAnderson RG Chapman KD (2010) Disruption of the Arabidopsis CGI-58 homologue produces Chanarin-Dorfman-like lipid droplet accumu-lation in plants Proc Natl Acad Sci USA 107 17833ndash17838

Kamisugi Y Mitsuya S El-Shami M Knight CD Cuming AC Baker A(2016) Giant peroxisomes in a moss (Physcomitrella patens) peroxisomalbiogenesis factor 11 mutant New Phytol 209 576ndash589

Kao YT Bartel B (2015) Elevated growth temperature decreases levels ofthe PEX5 peroxisome-targeting signal receptor and ameliorates defectsof Arabidopsis mutants with an impaired PEX4 ubiquitin-conjugatingenzyme BMC Plant Biol 15 224

Kao YT Fleming WA Ventura MJ Bartel B (2016) Genetic interactionsbetween PEROXIN12 and other peroxisome-associated ubiquitinationcomponents Plant Physiol 172 1643ndash1656

Kataya AR Heidari B Hagen L Kommedal R Slupphaug G Lillo C(2015) Protein phosphatase 2A holoenzyme is targeted to peroxisomesby piggybacking and positively affects peroxisomal b-oxidation PlantPhysiol 167 493ndash506

Kaur N Zhao Q Xie Q Hu J (2013) Arabidopsis RING peroxins are E3ubiquitin ligases that interact with two homologous ubiquitin receptorproteins(F) J Integr Plant Biol 55 108ndash120

Kelly AA van Erp H Quettier AL Shaw E Menard G Kurup S Eastmond PJ(2013) The sugar-dependent1 lipase limits triacylglycerol accumulation invegetative tissues of Arabidopsis Plant Physiol 162 1282ndash1289

Kemper C Habib SJ Engl G Heckmeyer P Dimmer KS Rapaport D(2008) Integration of tail-anchored proteins into the mitochondrial outermembrane does not require any known import components J Cell Sci121 1990ndash1998

Kerchev P Waszczak C Lewandowska A Willems P Shapiguzov A Li ZAlseekh S Muumlhlenbock P Hoeberichts FA Huang J van der Kelen KKangasjaumlrvi J et al (2016) Lack of GLYCOLATE OXIDASE1 but notGLYCOLATE OXIDASE2 attenuates the photorespiratory phenotype ofCATALASE2-deficient Arabidopsis Plant Physiol 171 1704ndash1719

Khan BR Adham AR Zolman BK (2012) Peroxisomal Acyl-CoA oxidase4 activity differs between Arabidopsis accessions Plant Mol Biol 78 45ndash58

Khan BR Zolman BK (2010) pex5 Mutants that differentially disrupt PTS1and PTS2 peroxisomal matrix protein import in Arabidopsis PlantPhysiol 154 1602ndash1615

Kim J Lee H Lee HN Kim SH Shin KD Chung T (2013) Autophagy-related proteins are required for degradation of peroxisomes in Arabi-dopsis hypocotyls during seedling growth Plant Cell 25 4956ndash4966

Kim PK Hailey DW Mullen RT Lippincott-Schwartz J (2008) Ubiquitinsignals autophagic degradation of cytosolic proteins and peroxisomesProc Natl Acad Sci USA 105 20567ndash20574

Kim PK Mullen RT Schumann U Lippincott-Schwartz J (2006) The or-igin and maintenance of mammalian peroxisomes involves a de novoPEX16-dependent pathway from the ER J Cell Biol 173 521ndash532

Klempien A Kaminaga Y Qualley A Nagegowda DA Widhalm JROrlova I Shasany AK Taguchi G Kish CM Cooper BR DrsquoAuria JCRhodes D et al (2012) Contribution of CoA ligases to benzenoid bio-synthesis in petunia flowers Plant Cell 24 2015ndash2030

Korasick DA Enders TA Strader LC (2013) Auxin biosynthesis and stor-age forms J Exp Bot 64 2541ndash2555

Kunz HH Scharnewski M Feussner K Feussner I Fluumlgge UI Fulda MGierthM (2009) The ABC transporter PXA1 and peroxisomal b-oxidation arevital for metabolism in mature leaves of Arabidopsis during extended dark-ness Plant Cell 21 2733ndash2749

Landrum M Smertenko A Edwards R Hussey PJ Steel PG (2010) BODIPYprobes to study peroxisome dynamics in vivo Plant J 62 529ndash538

Lanyon-Hogg T Hooper J Gunn S Warriner SL Baker A (2014) PEX14binding to Arabidopsis PEX5 has differential effects on PTS1 and PTS2cargo occupancy of the receptor FEBS Lett 588 2223ndash2229

Law KB Bronte-Tinkew D Di Pietro E Snowden A Jones RO Moser ABrumell JH Braverman N Kim PK (2017) The peroxisomal AAA ATPasecomplex prevents pexophagy and development of peroxisome biogenesisdisorders Autophagy 13 868ndash884

Lee JR Jang HH Park JH Jung JH Lee SS Park SK Chi YH Moon JC LeeYM Kim SY Kim JY Yun DJ et al (2006) Cloning of two splice variants ofthe rice PTS1 receptor OsPex5pL and OsPex5pS and their functional char-acterization using pex5-deficient yeast and Arabidopsis Plant J 47 457ndash466

Lee MS Mullen RT Trelease RN (1997) Oilseed isocitrate lyases lackingtheir essential type 1 peroxisomal targeting signal are piggybacked toglyoxysomes Plant Cell 9 185ndash197

Lee MY Sumpter R Jr Zou Z Sirasanagandla S Wei Y Mishra PRosewich H Crane DI Levine B (2017) Peroxisomal protein PEX13functions in selective autophagy EMBO Rep 18 48ndash60

Lee S Kaminaga Y Cooper B Pichersky E Dudareva N Chapple C (2012)Benzoylation and sinapoylation of glucosinolate R-groups in Arabi-dopsis Plant J 72 411ndash422

Leterrier M Barroso JB Valderrama R Begara-Morales JC Saacutenchez-Calvo B Chaki M Luque F Vintildeegla B Palma JM Corpas FJ (2016)Peroxisomal NADP-isocitrate dehydrogenase is required for Arabidopsisstomatal movement Protoplasma 253 403ndash415

Li F Vierstra RD (2012) Autophagy a multifaceted intracellular system forbulk and selective recycling Trends Plant Sci 17 526ndash537

Li J Hu J (2015) Using co-expression analysis and stress-based screens touncover Arabidopsis peroxisomal proteins involved in drought responsePLoS One 10 e0137762

Li XR Li HJ Yuan L Liu M Shi DQ Liu J Yang WC (2014) ArabidopsisDAYUABERRANT PEROXISOME MORPHOLOGY9 is a key regulatorof peroxisome biogenesis and plays critical roles during pollen matu-ration and germination in planta Plant Cell 26 619ndash635

Lin Y Sun L Nguyen LV Rachubinski RA Goodman HM (1999) ThePex16p homolog SSE1 and storage organelle formation in Arabidopsisseeds Science 284 328ndash330

Ling Q Huang W Baldwin A Jarvis P (2012) Chloroplast biogenesis isregulated by direct action of the ubiquitin-proteasome system Science338 655ndash659

Ling Q Jarvis P (2015) Regulation of chloroplast protein import by theubiquitin E3 ligase SP1 is important for stress tolerance in plants CurrBiol 25 2527ndash2534


Kao et al


Ling Q Li N Jarvis P (2017) Chloroplast ubiquitin E3 ligase SP1 does itreally function in peroxisomes Plant Physiol 175 586ndash588

Lingard MJ Bartel B (2009) Arabidopsis LON2 is necessary for peroxisomalfunction and sustained matrix protein import Plant Physiol 151 1354ndash1365

Lingard MJ Gidda SK Bingham S Rothstein SJ Mullen RT TreleaseRN (2008) Arabidopsis PEROXIN11c-e FISSION1b and DYNAMIN-RELATED PROTEIN3A cooperate in cell cycle-associated replicationof peroxisomes Plant Cell 20 1567ndash1585

Lingard MJ Monroe-Augustus M Bartel B (2009) Peroxisome-associatedmatrix protein degradation in Arabidopsis Proc Natl Acad Sci USA 1064561ndash4566

Lingard MJ Trelease RN (2006) Five Arabidopsis peroxin 11 homologs in-dividually promote peroxisome elongation duplication or aggregationJ Cell Sci 119 1961ndash1972

Lingner T Kataya AR Antonicelli GE Benichou A Nilssen K Chen XYSiemsen T Morgenstern B Meinicke P Reumann S (2011) Identifi-cation of novel plant peroxisomal targeting signals by a combination ofmachine learning methods and in vivo subcellular targeting analysesPlant Cell 23 1556ndash1572

Liu WC Han TT Yuan HM Yu ZD Zhang LY Zhang BL Zhai S ZhengSQ Lu YT (2017) CATALASE2 functions for seedling post-germinativegrowth by scavenging H2O2 and stimulating ACX23 activity in Ara-bidopsis Plant Cell Environ 40 2720ndash2728

Mano S Hayashi M Nishimura M (1999) Light regulates alternativesplicing of hydroxypyruvate reductase in pumpkin Plant J 17 309ndash320

Mano S Nakamori C Kondo M Hayashi M Nishimura M (2004) AnArabidopsis dynamin-related protein DRP3A controls both peroxisomaland mitochondrial division Plant J 38 487ndash498

Mano S Nakamori C Nito K Kondo M Nishimura M (2006) The Arabi-dopsis pex12 and pex13 mutants are defective in both PTS1- and PTS2-dependent protein transport to peroxisomes Plant J 47 604ndash618

Marzioch M Erdmann R Veenhuis M Kunau WH (1994) PAS7 encodes anovel yeast member of the WD-40 protein family essential for import of3-oxoacyl-CoA thiolase a PTS2-containing protein into peroxisomesEMBO J 13 4908ndash4918

Matsumoto N Tamura S Fujiki Y (2003) The pathogenic peroxin Pex26precruits the Pex1p-Pex6p AAA ATPase complexes to peroxisomes NatCell Biol 5 454ndash460

McDonnell MM Burkhart SE Stoddard JM Wright ZJ Strader LCBartel B (2016) The early-acting peroxin PEX19 is redundantly encodedfarnesylated and essential for viability in Arabidopsis thaliana PLoS One11 e0148335

McLachlan DH Lan J Geilfus CM Dodd AN Larson T Baker A HotilderakH Kollist H He Z Graham I Mickelbart MV Hetherington AM(2016) The breakdown of stored triacylglycerols is required during light-induced stomatal opening Curr Biol 26 707ndash712

McNew JA Goodman JM (1994) An oligomeric protein is imported intoperoxisomes in vivo J Cell Biol 127 1245ndash1257

Meinecke M Cizmowski C Schliebs W Kruumlger V Beck S Wagner RErdmann R (2010) The peroxisomal importomer constitutes a large andhighly dynamic pore Nat Cell Biol 12 273ndash277

Mendiondo GM Medhurst A van Roermund CW Zhang X DevonshireJ Scholefield D Fernaacutendez J Axcell B Ramsay L Waterham HRWaugh R Theodoulou FL et al (2014) Barley has two peroxisomal ABCtransporters with multiple functions in b-oxidation J Exp Bot 65 4833ndash4847

Mitsuya S El-Shami M Sparkes IA Charlton WL Lousa CdeM JohnsonB Baker A (2010) Salt stress causes peroxisome proliferation but in-ducing peroxisome proliferation does not improve NaCl tolerance inArabidopsis thaliana PLoS One 5 e9408

Miyauchi-Nanri Y Mukai S Kuroda K Fujiki Y (2014) CUL4A-DDB1-Rbx1 E3 ligase controls the quality of the PTS2 receptor Pex7p Bio-chem J 463 65ndash74

Monroe-Augustus M Ramoacuten NM Ratzel SE Lingard MJ ChristensenSE Murali C Bartel B (2011) Matrix proteins are inefficiently importedinto Arabidopsis peroxisomes lacking the receptor-docking peroxinPEX14 Plant Mol Biol 77 1ndash15

Motley AM Hettema EH Ketting R Plasterk R Tabak HF (2000) Cae-norhabditis elegans has a single pathway to target matrix proteins toperoxisomes EMBO Rep 1 40ndash46

Motley AM Nuttall JM Hettema EH (2012) Pex3-anchored Atg36 tags perox-isomes for degradation in Saccharomyces cerevisiae EMBO J 31 2852ndash2868

Nishimura M Yamaguchi J Mori H Akazawa T Yokota S (1986) Im-munocytochemical analysis shows that glyoxysomes are directly trans-formed to leaf peroxisomes during greening of pumpkin cotyledonsPlant Physiol 81 313ndash316

Nito K Hayashi M Nishimura M (2002) Direct interaction and determi-nation of binding domains among peroxisomal import factors in Ara-bidopsis thaliana Plant Cell Physiol 43 355ndash366

Nito K Kamigaki A Kondo M Hayashi M Nishimura M (2007) Functionalclassification of Arabidopsis peroxisome biogenesis factors proposed fromanalyses of knockdown mutants Plant Cell Physiol 48 763ndash774

Nolan TM Brennan B Yang M Chen J Zhang M Li Z Wang X BasshamDC Walley J Yin Y (2017) Selective autophagy of BES1 mediated byDSK2 balances plant growth and survival Dev Cell 41 33ndash46e7

Nuttall JM Motley AM Hettema EH (2014) Deficiency of the exportomercomponents Pex1 Pex6 and Pex15 causes enhanced pexophagy inSaccharomyces cerevisiae Autophagy 10 835ndash845

Nyathi Y De Marcos Lousa C van Roermund CW Wanders RJA Johnson BBaldwin SA Theodoulou FL Baker A (2010) The Arabidopsis peroxisomalABC transporter comatose complements the Saccharomyces cerevisiae pxa1pxa2Dmutant for metabolism of long-chain fatty acids and exhibits fatty acyl-CoA-stimulated ATPase activity J Biol Chem 285 29892ndash29902

Nyathi Y Zhang X Baldwin JM Bernhardt K Johnson B Baldwin SATheodoulou FL Baker A (2012) Pseudo half-molecules of the ABCtransporter COMATOSE bind Pex19 and target to peroxisomes inde-pendently but are both required for activity FEBS Lett 586 2280ndash2286

Oikawa K Matsunaga S Mano S Kondo M Yamada K Hayashi MKagawa T Kadota A Sakamoto W Higashi S Watanabe M Mitsui Tet al (2015) Physical interaction between peroxisomes and chloroplastselucidated by in situ laser analysis Nat Plants 1 15035

Okumoto K Noda H Fujiki Y (2014) Distinct modes of ubiquitination ofperoxisome-targeting signal type 1 (PTS1) receptor Pex5p regulate PTS1protein import J Biol Chem 289 14089ndash14108

Orth T Reumann S Zhang X Fan J Wenzel D Quan S Hu J (2007) ThePEROXIN11 protein family controls peroxisome proliferation in Arabi-dopsis Plant Cell 19 333ndash350

Otera H Okumoto K Tateishi K Ikoma Y Matsuda E Nishimura MTsukamoto T Osumi T Ohashi K Higuchi O Fujiki Y (1998) Perox-isome targeting signal type 1 (PTS1) receptor is involved in import ofboth PTS1 and PTS2 studies with PEX5-defective CHO cell mutantsMol Cell Biol 18 388ndash399

Otera H Setoguchi K Hamasaki M Kumashiro T Shimizu N Fujiki Y(2002) Peroxisomal targeting signal receptor Pex5p interacts withcargoes and import machinery components in a spatiotemporally dif-ferentiated manner conserved Pex5p WXXXFY motifs are critical formatrix protein import Mol Cell Biol 22 1639ndash1655

Pan D Nakatsu T Kato H (2013) Crystal structure of peroxisomal targetingsignal-2 bound to its receptor complex Pex7p-Pex21p Nat Struct MolBiol 20 987ndash993

Pan R Satkovich J Hu J (2016) E3 ubiquitin ligase SP1 regulates peroxi-some biogenesis in Arabidopsis Proc Natl Acad Sci USA 113 E7307ndashE7316

Park S Gidda SK James CN Horn PJ Khuu N Seay DC KeereetaweepJ Chapman KD Mullen RT Dyer JM (2013) The ab hydrolase CGI-58and peroxisomal transport protein PXA1 coregulate lipid homeostasisand signaling in Arabidopsis Plant Cell 25 1726ndash1739

Pires JR Hong X Brockmann C Volkmer-Engert R Schneider-Mergener JOschkinat H Erdmann R (2003) The ScPex13p SH3 domain exposes twodistinct binding sites for Pex5p and Pex14p J Mol Biol 326 1427ndash1435

Platta HW El Magraoui F Baumlumer BE Schlee D Girzalsky W ErdmannR (2009) Pex2 and pex12 function as protein-ubiquitin ligases in per-oxisomal protein import Mol Cell Biol 29 5505ndash5516

Pracharoenwattana I Cornah JE Smith SM (2007) Arabidopsis peroxisomalmalate dehydrogenase functions in b-oxidation but not in the glyoxylatecycle Plant J 50 381ndash390

Prestele J Hierl G Scherling C Hetkamp S Schwechheimer C Isono EWeckwerth W Wanner G Gietl C (2010) Different functions of theC3HC4 zinc RING finger peroxins PEX10 PEX2 and PEX12 in peroxi-some formation and matrix protein import Proc Natl Acad Sci USA 10714915ndash14920

Pyc M Cai Y Greer MS Yurchenko O Chapman KD Dyer JM MullenRT (2017) Turning over a new leaf in lipid droplet biology Trends PlantSci 22 596ndash609




Qualley AV Widhalm JR Adebesin F Kish CM Dudareva N (2012)Completion of the core b-oxidative pathway of benzoic acid biosyn-thesis in plants Proc Natl Acad Sci USA 109 16383ndash16388

Quan S Yang P Cassin-Ross G Kaur N Switzenberg R Aung K Li J HuJ (2013) Proteome analysis of peroxisomes from etiolated Arabidopsisseedlings identifies a peroxisomal protease involved in b-oxidation anddevelopment Plant Physiol 163 1518ndash1538

Queval G Issakidis-Bourguet E Hoeberichts FA Vandorpe M GakiegravereB Vanacker H Miginiac-Maslow M van Breusegem F Noctor G(2007) Conditional oxidative stress responses in the Arabidopsis photo-respiratory mutant cat2 demonstrate that redox state is a key modulatorof daylength-dependent gene expression and define photoperiod as acrucial factor in the regulation of H2O2-induced cell death Plant J 52640ndash657

Ramoacuten NM Bartel B (2010) Interdependence of the peroxisome-targetingreceptors in Arabidopsis thaliana PEX7 facilitates PEX5 accumulation andimport of PTS1 cargo into peroxisomes Mol Biol Cell 21 1263ndash1271

Ratzel SE Lingard MJ Woodward AW Bartel B (2011) Reducing PEX13expression ameliorates physiological defects of late-acting peroxin mu-tants Traffic 12 121ndash134

Reumann S (2004) Specification of the peroxisome targeting signals type1 and type 2 of plant peroxisomes by bioinformatics analyses PlantPhysiol 135 783ndash800

Reumann S (2011) Toward a definition of the complete proteome of plantperoxisomes where experimental proteomics must be complemented bybioinformatics Proteomics 11 1764ndash1779

Reumann S Bartel B (2016) Plant peroxisomes recent discoveries infunctional complexity organelle homeostasis and morphological dy-namics Curr Opin Plant Biol 34 17ndash26

Reumann S Buchwald D Lingner T (2012) PredPlantPTS1 a web serverfor the prediction of plant peroxisomal proteins Front Plant Sci 3 194

Reumann S Quan S Aung K Yang P Manandhar-Shrestha K HolbrookD Linka N Switzenberg R Wilkerson CG Weber AP Olsen LJ Hu J(2009) In-depth proteome analysis of Arabidopsis leaf peroxisomescombined with in vivo subcellular targeting verification indicates novelmetabolic and regulatory functions of peroxisomes Plant Physiol 150125ndash143

Rinaldi MA Fleming WA Gonzalez KL Park J Ventura MJ Patel ABBartel B (2017) The PEX1 ATPase stabilizes PEX6 and plays essentialroles in peroxisome biology Plant Physiol 174 2231ndash2247

Rinaldi MA Patel AB Park J Lee K Strader LC Bartel B (2016) The rolesof b-oxidation and cofactor homeostasis in peroxisome distribution andfunction in Arabidopsis thaliana Genetics 204 1089ndash1115

Rodrigues TA Alencastre IS Francisco T Brites P Fransen M Grou CPAzevedo JE (2014) A PEX7-centered perspective on the peroxisomaltargeting signal type 2-mediated protein import pathway Mol Cell Biol34 2917ndash2928

Rodriacuteguez-Serrano M Romero-Puertas MC Sanz-Fernaacutendez M Hu JSandalio LM (2016) Peroxisomes extend peroxules in a fast response tostress via a reactive oxygen species-mediated induction of the peroxinPEX11a Plant Physiol 171 1665ndash1674

Rottensteiner H Kramer A Lorenzen S Stein K Landgraf C Volkmer-Engert R Erdmann R (2004) Peroxisomal membrane proteins containcommon Pex19p-binding sites that are an integral part of their targetingsignals Mol Biol Cell 15 3406ndash3417

Rylott EL Rogers CA Gilday AD Edgell T Larson TR Graham IA (2003)Arabidopsis mutants in short- and medium-chain acyl-CoA oxidase ac-tivities accumulate acyl-CoAs and reveal that fatty acid b-oxidation isessential for embryo development J Biol Chem 278 21370ndash21377

Sargent G van Zutphen T Shatseva T Zhang L Di Giovanni VBandsma R Kim PK (2016) PEX2 is the E3 ubiquitin ligase required forpexophagy during starvation J Cell Biol 214 677ndash690

Sautter C (1986) Microbody transition in greening watermelon cotyledonsdouble immunocytochemical labeling of isocitrate lyase and hydrox-ypyruvate reductase Planta 167 491ndash503

Schell-Steven A Stein K Amoros M Landgraf C Volkmer-Engert RRottensteiner H Erdmann R (2005) Identification of a novel intra-peroxisomal pex14-binding site in pex13 association of pex13 with thedocking complex is essential for peroxisomal matrix protein import MolCell Biol 25 3007ndash3018

Schliebs W Girzalsky W Erdmann R (2010) Peroxisomal protein importand ERAD variations on a common theme Nat Rev Mol Cell Biol 11885ndash890

Schrul B Kopito RR (2016) Peroxin-dependent targeting of a lipid-droplet-destined membrane protein to ER subdomains Nat Cell Biol 18 740ndash751

Schuhmann H Huesgen PF Gietl C Adamska I (2008) The DEG15 serineprotease cleaves peroxisomal targeting signal 2-containing proteins inArabidopsis Plant Physiol 148 1847ndash1856

Schumann U Prestele J OrsquoGeen H Brueggeman R Wanner G Gietl C(2007) Requirement of the C3HC4 zinc RING finger of the ArabidopsisPEX10 for photorespiration and leaf peroxisome contact with chloro-plasts Proc Natl Acad Sci USA 104 1069ndash1074

Schumann U Wanner G Veenhuis M Schmid M Gietl C (2003) AthPEX10a nuclear gene essential for peroxisome and storage organelle formationduring Arabidopsis embryogenesis Proc Natl Acad Sci USA 100 9626ndash9631

Scott I Tobin AK Logan DC (2006) BIGYIN an orthologue of human andyeast FIS1 genes functions in the control of mitochondrial size andnumber in Arabidopsis thaliana J Exp Bot 57 1275ndash1280

Shibata M Oikawa K Yoshimoto K Kondo M Mano S Yamada KHayashi M Sakamoto W Ohsumi Y Nishimura M (2013) Highly ox-idized peroxisomes are selectively degraded via autophagy in Arabi-dopsis Plant Cell 25 4967ndash4983

Sinclair AM Trobacher CP Mathur N Greenwood JS Mathur J (2009)Peroxule extension over ER-defined paths constitutes a rapid subcellularresponse to hydroxyl stress Plant J 59 231ndash242

Skoulding NS Chowdhary G Deus MJ Baker A Reumann S WarrinerSL (2015) Experimental validation of plant peroxisomal targeting pre-diction algorithms by systematic comparison of in vivo import efficiencyand in vitro PTS1 binding affinity J Mol Biol 427 1085ndash1101

Slocombe SP Cornah J Pinfield-Wells H Soady K Zhang Q Gilday ADyer JM Graham IA (2009) Oil accumulation in leaves directed bymodification of fatty acid breakdown and lipid synthesis pathwaysPlant Biotechnol J 7 694ndash703

Sparkes IA Brandizzi F Slocombe SP El-Shami M Hawes C Baker A(2003) An Arabidopsis pex10 null mutant is embryo lethal implicatingperoxisomes in an essential role during plant embryogenesis PlantPhysiol 133 1809ndash1819

Stein K Schell-Steven A Erdmann R Rottensteiner H (2002) Interactionsof Pex7p and Pex18pPex21p with the peroxisomal docking machineryimplications for the first steps in PTS2 protein import Mol Cell Biol 226056ndash6069

Strader LC Bartel B (2009) The Arabidopsis PLEIOTROPIC DRUG RE-SISTANCE8ABCG36 ATP binding cassette transporter modulatessensitivity to the auxin precursor indole-3-butyric acid Plant Cell 211992ndash2007

Strader LC Bartel B (2011) Transport and metabolism of the endogenousauxin precursor indole-3-butyric acid Mol Plant 4 477ndash486

Strader LC Culler AH Cohen JD Bartel B (2010) Conversion of endog-enous indole-3-butyric acid to indole-3-acetic acid drives cell expansionin Arabidopsis seedlings Plant Physiol 153 1577ndash1586

Strader LC Wheeler DL Christensen SE Berens JC Cohen JD RampeyRA Bartel B (2011) Multiple facets of Arabidopsis seedling developmentrequire indole-3-butyric acid-derived auxin Plant Cell 23 984ndash999

Sugiura A Mattie S Prudent J McBride HM (2017) Newly born peroxi-somes are a hybrid of mitochondrial and ER-derived pre-peroxisomesNature 542 251ndash254

Tamura S Matsumoto N Takeba R Fujiki Y (2014) AAA peroxins andtheir recruiter Pex26p modulate the interactions of peroxins involved inperoxisomal protein import J Biol Chem 289 24336ndash24346

Thazar-Poulot N Miquel M Fobis-Loisy I Gaude T (2015) Peroxisomeextensions deliver the Arabidopsis SDP1 lipase to oil bodies Proc NatlAcad Sci USA 112 4158ndash4163

Timm S Bauwe H (2013) The variety of photorespiratory phenotypes -employing the current status for future research directions on photo-respiration Plant Biol (Stuttg) 15 737ndash747

Titus DE Becker WM (1985) Investigation of the glyoxysome-peroxisometransition in germinating cucumber cotyledons using double-label im-munoelectron microscopy J Cell Biol 101 1288ndash1299

Urquhart AJ Kennedy D Gould SJ Crane DI (2000) Interaction of Pex5pthe type 1 peroxisome targeting signal receptor with the peroxisomalmembrane proteins Pex14p and Pex13p J Biol Chem 275 4127ndash4136

van der Leij I Franse MM Elgersma Y Distel B Tabak HF (1993) PAS10is a tetratricopeptide-repeat protein that is essential for the import ofmost matrix proteins into peroxisomes of Saccharomyces cerevisiae ProcNatl Acad Sci USA 90 11782ndash11786


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van der Zand A Braakman I Tabak HF (2010) Peroxisomal membraneproteins insert into the endoplasmic reticulum Mol Biol Cell 21 2057ndash2065

van der Zand A Gent J Braakman I Tabak HF (2012) Biochemicallydistinct vesicles from the endoplasmic reticulum fuse to form peroxi-somes Cell 149 397ndash409

van Moerkercke A Schauvinhold I Pichersky E Haring MA SchuurinkRC (2009) A plant thiolase involved in benzoic acid biosynthesis andvolatile benzenoid production Plant J 60 292ndash302

van Roermund CW Schroers MGWiese J Facchinelli F Kurz S Wilkinson SCharton L Wanders RJ Waterham HR Weber AP Link N (2016) Theperoxisomal NAD carrier from Arabidopsis imports NAD in exchangewith AMP Plant Physiol 171 2127ndash2139

Wang J Wang Y Gao C Jiang L Guo D (2017) PPero a computationalmodel for plant PTS1 type peroxisomal protein prediction PLoS One 12e0168912

Wasternack C Hause B (2013) Jasmonates biosynthesis perception signaltransduction and action in plant stress response growth and develop-ment An update to the 2007 review in Annals of Botany Ann Bot 1111021ndash1058

Waszczak C Kerchev PI Muumlhlenbock P Hoeberichts FA van der KelenK Mhamdi A Willems P Denecker J Kumpf RP Noctor G MessensJ van Breusegem F (2016) SHORT-ROOT deficiency alleviates the celldeath phenotype of the Arabidopsis catalase2 mutant under photorespiration-promoting conditions Plant Cell 28 1844ndash1859

Woodward AW Bartel B (2005) The Arabidopsis peroxisomal targetingsignal type 2 receptor PEX7 is necessary for peroxisome function anddependent on PEX5 Mol Biol Cell 16 573ndash583

Woodward AW Fleming WA Burkhart SE Ratzel SE Bjornson M BartelB (2014) A viable Arabidopsis pex13 missense allele confers severe per-oxisomal defects and decreases PEX5 association with peroxisomesPlant Mol Biol 86 201ndash214

Wu TM Lin KC Liau WS Chao YY Yang LH Chen SY Lu CA Hong CY(2016) A set of GFP-based organelle marker lines combined with DsRed-based gateway vectors for subcellular localization study in rice (Oryzasativa L) Plant Mol Biol 90 107ndash115

Xie Q Tzfadia O Levy M Weithorn E Peled-Zehavi H van Parys T vande Peer Y Galili G (2016) hfAIM a reliable bioinformatics approach forin silico genome-wide identification of autophagy-associated Atg8-interacting motifs in various organisms Autophagy 12 876ndash887

Xu L Zhao H Ruan W Deng M Wang F Peng J Luo J Chen Z Yi K(2017) ABNORMAL INFLORESCENCE MERISTEM1 functions in sali-cylic acid biosynthesis to maintain proper reactive oxygen species levelsfor root meristem activity in rice Plant Cell 29 560ndash574

Yalpani N Leon J Lawton MA Raskin I (1993) Pathway of salicylic acidbiosynthesis in healthy and virus-inoculated tobacco Plant Physiol 103315ndash321

Yoshimoto K Shibata M Kondo M Oikawa K Sato M Toyooka K ShirasuK Nishimura M Ohsumi Y (2014) Organ-specific quality control of plantperoxisomes is mediated by autophagy J Cell Sci 127 1161ndash1168

Young PG Bartel B (2016) Pexophagy and peroxisomal protein turnover inplants Biochim Biophys Acta 1863 999ndash1005

Yuan HM Liu WC Lu YT (2017) CATALASE2 coordinates SA-mediatedrepression of both auxin accumulation and JA biosynthesis in plantdefenses Cell Host Microbe 21 143ndash155

Zhang J Tripathi DN Jing J Alexander A Kim J Powell RT Dere RTait-Mulder J Lee JH Paull TT Pandita RK Charaka VK et al (2015)ATM functions at the peroxisome to induce pexophagy in response toROS Nat Cell Biol 17 1259ndash1269

Zhang X Hu J (2010) The Arabidopsis chloroplast division proteinDYNAMIN-RELATED PROTEIN5B also mediates peroxisome divisionPlant Cell 22 431ndash442

Zhang X Hu J (2009) Two small protein families DYNAMIN-RELATEDPROTEIN3 and FISSION1 are required for peroxisome fission in Ara-bidopsis Plant J 57 146ndash159

Zolman BK Bartel B (2004) An Arabidopsis indole-3-butyric acid-responsemutant defective in PEROXIN6 an apparent ATPase implicated inperoxisomal function Proc Natl Acad Sci USA 101 1786ndash1791

Zolman BK Monroe-Augustus M Silva ID Bartel B (2005) Identificationand functional characterization of Arabidopsis PEROXIN4 and the in-teracting protein PEROXIN22 Plant Cell 17 3422ndash3435

Zolman BK Silva ID Bartel B (2001) The Arabidopsis pxa1 mutant is de-fective in an ATP-binding cassette transporter-like protein required forperoxisomal fatty acid b-oxidation Plant Physiol 127 1266ndash1278

Zolman BK Yoder A Bartel B (2000) Genetic analysis of indole-3-butyricacid responses in Arabidopsis thaliana reveals four mutant classes Ge-netics 156 1323ndash1337

Zutphen Tv Veenhuis M van der Klei IJ (2008) Pex14 is the sole com-ponent of the peroxisomal translocon that is required for pexophagyAutophagy 4 63ndash66




which can undergo additional b-oxidation roundsSeedling acetyl-CoA is further metabolized by peroxi-somal glyoxylate cycle enzymes into four-carbon dicar-boxylic acids which ultimately can be converted to Sucused for growth (for review see Graham 2008) Perox-isomes are the sole site of fatty acid b-oxidation in plants(for review see Graham 2008) and mutations in thegenes encoding PXA1 various b-oxidation enzymes orglyoxylate cycle enzymes confer seedling growth defectsthat are partially alleviated by providing a fixed carbonsource such as Suc (for review see Bartel et al 2014)MFP2 andAIM1 requireNAD+which is imported by thePXN peroxisomal NAD+ carrier and recycled by peroxi-somal NAD+-malate dehydrogenase (PMDH) and mon-odehydroascorbate reductase (MDAR4) Consequentlypmdh mdar4 and pxn mutants also display b-oxidationdefects (Eastmond 2007 Pracharoenwattana et al 2007Bernhardt et al 2012 Rinaldi et al 2016 van Roermundet al 2016)Oil bodies also known as lipid droplets compart-

mentalize neutral lipids and allow storage of largequantities of triacylglycerol in oilseeds (for review seePyc et al 2017) During germination and early seedlinggrowth peroxisomes associate with oil bodies (Chapmanand Trelease 1991 Hayashi et al 2001) to utilize seedenergy reserves (for review see Graham 2008) Oil bodytriacylglycerol is hydrolyzed to free fatty acids by the li-pase SUCROSEDEPENDENT1 (SDP1) (Eastmond 2006)which is delivered from peroxisomes to oil bodies withthe assistance of the Golgi retromer complex (Thazar-Poulot et al 2015) The fatty acyl-CoA transporter PXA1

also promotes peroxisome-oil body interactions (Cui et al2016) possibly facilitating peroxisomal invaginations dur-ing oil body consumption

Seedlings retain oil bodies when b-oxidation is im-paired Various mutants defective in b-oxidation theglyoxylate cycle or NADH reduction display peroxi-somes clustered near oil bodies after oil bodies are de-pleted in wild type (Germain et al 2001 Eastmond2007 Pracharoenwattana et al 2007 Cassin-Ross andHu 2014 Rinaldi et al 2016) Moreover diphenylmethylphosphonate confers triacylglycerol retention(Brown et al 2013) similar to sdp1 and pxa1 mutants(Eastmond 2006 Slocombe et al 2009 Kelly et al2013) The mechanism through which peroxisomal en-zyme dysfunction feeds back to prevents triacylglycerolmobilization is unknown

In addition to fueling germination oil bodies andperoxisomes collaborate to provide energy in leavesArabidopsis CGI-58 a homolog of a mammalian lipaseactivator (comparative gene identification-58) promotesPXA1 function in leaves but not in germinating seeds(Park et al 2013) and triacylglycerol accumulates in leafoil bodies in cgi-58 mutants (James et al 2010) More-over b-oxidation of triacylglycerol from stomatal oilbodies contributes to the ATP production necessary forstomatal opening upon transfer from dark to light(McLachlan et al 2016) When b-oxidation is slowed asin pxa1 sdp1 or cgi-58 mutants stomatal opening isimpeded (McLachlan et al 2016) Because environmentalstimuli such as light and temperature regulate stomatalaperture to control water and gas exchange (for review

Figure 1 Plant peroxisome functionsPeroxisomes house a variety of catabolicand biosynthetic reactions (Reumannand Bartel 2016) several of whichgenerate H2O2 and other ROS (orange)b-oxidation (red) is used to catabolizefatty acids (purple) and in the synthesisof several hormones (blue) PeroxisomalROS can be inactivated by catalase andotherenzymeswithin theperoxisomeorcanexit the peroxisomes to serve signaling rolesOPC83-oxo-2-(29-pentenyl)-cyclopentane-1-octanoic acidOPDA12-oxo-phytodienoicacid















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