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    296 297 298 299 300 301 302 303 304 305

    𝑚𝑖𝑡𝑜𝑐ℎ𝑜𝑛𝑑𝑟𝑖𝑎𝑙 𝑠𝑐𝑜𝑟𝑒

    = 𝑙𝑜𝑔2 (𝑃𝑚𝑖𝑡𝑜𝑐ℎ𝑜𝑛𝑑𝑟𝑖𝑎𝑙

    𝑃𝑛𝑜𝑛−𝑚𝑖𝑡𝑜𝑐ℎ𝑜𝑛𝑑𝑟𝑖𝑎𝑙) + ∑ 𝑙𝑜𝑔2 (

    𝑃(𝑑𝑎𝑡𝑎𝑖|𝑚𝑖𝑡𝑜𝑐ℎ𝑜𝑛𝑑𝑟𝑖𝑎𝑙)

    𝑃(𝑑𝑎𝑡𝑎𝑖|𝑛𝑜𝑛 − 𝑚𝑖𝑡𝑜𝑐ℎ𝑜𝑛𝑑𝑟𝑖𝑎𝑙))

    𝑛

    𝑖=1

    306

    𝑤𝑖𝑡ℎ 𝑃(𝑑𝑎𝑡𝑎𝑖|𝑚𝑖𝑡𝑜𝑐ℎ𝑜𝑛𝑑𝑟𝑖𝑎𝑙)

    𝑃(𝑑𝑎𝑡𝑎𝑖|𝑛𝑜𝑛 − 𝑚𝑖𝑡𝑜𝑐ℎ𝑜𝑛𝑑𝑟𝑖𝑎𝑙)=

    𝑚𝑖𝑡𝑜𝑐ℎ𝑜𝑛𝑑𝑟𝑖𝑎𝑙_𝑝𝑜𝑠𝑖𝑚𝑖𝑡𝑜𝑐ℎ𝑜𝑛𝑑𝑟𝑖𝑎𝑙_𝑛𝑒𝑔𝑖

    307 308 309 310 311 312 313 314 315 316 317 318 319 320

    𝑐𝐹𝐷𝑅 =1 − 𝑠𝑝𝑒𝑐𝑖𝑓𝑖𝑐𝑖𝑡𝑦

    1 − 𝑠𝑝𝑒𝑐𝑖𝑓𝑖𝑐𝑖𝑡𝑦 + 𝑠𝑒𝑛𝑠𝑖𝑡𝑖𝑣𝑖𝑡𝑦 ⋅ 𝑂𝑝𝑟𝑖𝑜𝑟321 322 323 324 325 326 327 328 329 330 331 332 333 334 335

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    743 REFERENCES 744 745 1. Gray MW, Burger G, Lang BF. Mitochondrial evolution. Science (New York, NY). 746 1999;283(5407):1476-81. 747 2. Burger G, Gray MW, Forget L, Lang BF. Strikingly bacteria-like and gene-rich 748 mitochondrial genomes throughout jakobid protists. Genome biology and evolution. 749 2013;5(2):418-38. 750 3. Wilson RJ, Williamson DH. Extrachromosomal DNA in the Apicomplexa. Microbiology 751 and molecular biology reviews : MMBR. 1997;61(1):1-16. 752 4. Makiuchi T, Nozaki T. Highly divergent mitochondrion-related organelles in 753 anaerobic parasitic protozoa. Biochimie. 2014;100:3-17. 754 5. Calvo SE, Clauser KR, Mootha VK. MitoCarta2.0: an updated inventory of mammalian 755 mitochondrial proteins. Nucleic acids research. 2016;44(D1):D1251-7. 756 6. Jedelský PL, Doležal P, Rada P, Pyrih J, Smíd O, Hrdý I, et al. The minimal proteome in 757 the reduced mitochondrion of the parasitic protist Giardia intestinalis. PloS one. 758 2011;6(2):e17285. 759 7. van Dooren GG, Stimmler LM, McFadden GI. Metabolic maps and functions of the 760 Plasmodium mitochondrion. FEMS microbiology reviews. 2006;30(4):596-630. 761 8. Aurrecoechea C, Brestelli J, Brunk BP, Dommer J, Fischer S, Gajria B, et al. PlasmoDB: 762 a functional genomic database for malaria parasites. Nucleic acids research. 763 2009;37(Database issue):D539-43. 764 9. Goodman CD, Siregar JE, Mollard V, Vega-Rodríguez J, Syafruddin D, Matsuoka H, et 765 al. Parasites resistant to the antimalarial atovaquone fail to transmit by mosquitoes. Science 766 (New York, NY). 2016;352(6283):349-53. 767 10. Sturm A, Mollard V, Cozijnsen A, Goodman CD, McFadden GI. Mitochondrial ATP 768 synthase is dispensable in blood-stage Plasmodium berghei rodent malaria but essential in 769 the mosquito phase. Proceedings of the National Academy of Sciences of the United States 770 of America. 2015;112(33):10216-23. 771

    .CC-BY-NC 4.0 International licenseperpetuity. It is made available under apreprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in

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    11. Painter HJ, Morrisey JM, Mather MW, Vaidya AB. Specific role of mitochondrial 772 electron transport in blood-stage Plasmodium falciparum. Nature. 2007;446(7131):88-91. 773 12. Evers F, Cabrera-Orefice A, Elurbe DM, Lindert MK-t, Boltryk SD, Voss TS, et al. 774 Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum. 775 bioRxiv. 2020:2020.10.05.326496. 776 13. Pastore C, Adinolfi S, Huynen MA, Rybin V, Martin S, Mayer M, et al. YfhJ, a 777 molecular adaptor in iron-sulfur cluster formation or a frataxin-like protein? Structure 778 (London, England : 1993). 2006;14(5):857-67. 779 14. Goldberg AV, Molik S, Tsaousis AD, Neumann K, Kuhnke G, Delbac F, et al. 780 Localization and functionality of microsporidian iron-sulphur cluster assembly proteins. 781 Nature. 2008;452(7187):624-8. 782 15. Seidi A, Muellner-Wong LS, Rajendran E, Tjhin ET, Dagley LF, Aw VY, et al. Elucidating 783 the mitochondrial proteome of Toxoplasma gondii reveals the presence of a divergent 784 cytochrome c oxidase. eLife. 2018;7. 785 16. Matz JM, Goosmann C, Matuschewski K, Kooij TWA. An Unusual Prohibitin Regulates 786 Malaria Parasite Mitochondrial Membrane Potential. Cell reports. 2018;23(3):756-67. 787 17. Fry M, Pudney M. Site of action of the antimalarial hydroxynaphthoquinone, 2-788 [trans-4-(4'-chlorophenyl) cyclohexyl]-3-hydroxy-1,4-naphthoquinone (566C80). Biochemical 789 pharmacology. 1992;43(7):1545-53. 790 18. Stocks PA, Barton V, Antoine T, Biagini GA, Ward SA, O'Neill PM. Novel inhibitors of 791 the Plasmodium falciparum electron transport chain. Parasitology. 2014;141(1):50-65. 792 19. Kobayashi T, Sato S, Takamiya S, Komaki-Yasuda K, Yano K, Hirata A, et al. 793 Mitochondria and apicoplast of Plasmodium falciparum: behaviour on subcellular 794 fractionation and the implication. Mitochondrion. 2007;7(1-2):125-32. 795 20. Seeber F, Limenitakis J, Soldati-Favre D. Apicomplexan mitochondrial metabolism: a 796 story of gains, losses and retentions. Trends in parasitology. 2008;24(10):468-78. 797 21. Barylyuk K, Koreny L, Ke H, Butterworth S, Crook OM, Lassadi I, et al. A 798 Comprehensive Subcellular Atlas of the Toxoplasma Proteome via hyperLOPIT Provides 799 Spatial Context for Protein Functions. Cell Host Microbe. 2020;28(5):752-66.e9. 800 22. Jansen R, Yu H, Greenbaum D, Kluger Y, Krogan NJ, Chung S, et al. A Bayesian 801 networks approach for predicting protein-protein interactions from genomic data. Science 802 (New York, NY). 2003;302(5644):449-53. 803 23. van der Lee R, Feng Q, Langereis MA, Ter Horst R, Szklarczyk R, Netea MG, et al. 804 Integrative Genomics-Based Discovery of Novel Regulators of the Innate Antiviral Response. 805 PLoS computational biology. 2015;11(10):e1004553. 806 24. Meerstein-Kessel L, van der Lee R, Stone W, Lanke K, Baker DA, Alano P, et al. 807 Probabilistic data integration identifies reliable gametocyte-specific proteins and transcripts 808 in malaria parasites. Scientific reports. 2018;8(1):410. 809 25. van Esveld SL, Cansız-Arda Ş, Hensen F, van der Lee R, Huynen MA, Spelbrink JN. A 810 Combined Mass Spectrometry and Data Integration Approach to Predict the Mitochondrial 811 Poly(A) RNA Interacting Proteome. Frontiers in cell and developmental biology. 2019;7:283. 812 26. Woodcroft BJ, McMillan PJ, Dekiwadia C, Tilley L, Ralph SA. Determination of protein 813 subcellular localization in apicomplexan parasites. Trends in parasitology. 2012;28(12):546-814 54. 815 27. Günther S, Wallace L, Patzewitz EM, McMillan PJ, Storm J, Wrenger C, et al. 816 Apicoplast lipoic acid protein ligase B is not essential for Plasmodium falciparum. PLoS 817 pathogens. 2007;3(12):e189. 818

    .CC-BY-NC 4.0 International licenseperpetuity. It is made available under apreprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in

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  • 22

    28. Read M, Müller IB, Mitchell SL, Sims PF, Hyde JE. Dynamic subcellular localization of 819 isoforms of the folate pathway enzyme serine hydroxymethyltransferase (SHMT) through 820 the erythrocytic cycle of Plasmodium falciparum. Malaria journal. 2010;9:351. 821 29. Li Y, Calvo SE, Gutman R, Liu JS, Mootha VK. Expansion of biological pathways based 822 on evolutionary inference. Cell. 2014;158(1):213-25. 823 30. Verma R, Varshney GC, Raghava GP. Prediction of mitochondrial proteins of malaria 824 parasite using split amino acid composition and PSSM profile. Amino acids. 2010;39(1):101-825 10. 826 31. Foth BJ, Ralph SA, Tonkin CJ, Struck NS, Fraunholz M, Roos DS, et al. Dissecting 827 apicoplast targeting in the malaria parasite Plasmodium falciparum. Science (New York, NY). 828 2003;299(5607):705-8. 829 32. Baughman JM, Nilsson R, Gohil VM, Arlow DH, Gauhar Z, Mootha VK. A 830 computational screen for regulators of oxidative phosphorylation implicates SLIRP in 831 mitochondrial RNA homeostasis. PLoS genetics. 2009;5(8):e1000590. 832 33. Szklarczyk R, Megchelenbrink W, Cizek P, Ledent M, Velemans G, Szklarczyk D, et al. 833 WeGET: predicting new genes for molecular systems by weighted co-expression. Nucleic 834 acids research. 2016;44(D1):D567-73. 835 34. Mulvey CM, Breckels LM, Geladaki A, Britovšek NK, Nightingale DJH, Christoforou A, 836 et al. Using hyperLOPIT to perform high-resolution mapping of the spatial proteome. Nature 837 protocols. 2017;12(6):1110-35. 838 35. Christoforou A, Mulvey CM, Breckels LM, Geladaki A, Hurrell T, Hayward PC, et al. A 839 draft map of the mouse pluripotent stem cell spatial proteome. Nature communications. 840 2016;7:8992. 841 36. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search 842 tool. Journal of molecular biology. 1990;215(3):403-10. 843 37. Zimmermann L, Stephens A, Nam SZ, Rau D, Kübler J, Lozajic M, et al. A Completely 844 Reimplemented MPI Bioinformatics Toolkit with a New HHpred Server at its Core. Journal of 845 molecular biology. 2018;430(15):2237-43. 846 38. Szklarczyk R, Huynen MA. Expansion of the human mitochondrial proteome by intra- 847 and inter-compartmental protein duplication. Genome biology. 2009;10(11):R135. 848 39. Li L, Stoeckert CJ, Jr., Roos DS. OrthoMCL: identification of ortholog groups for 849 eukaryotic genomes. Genome research. 2003;13(9):2178-89. 850 40. Rao RS, Salvato F, Thal B, Eubel H, Thelen JJ, Møller IM. The proteome of higher plant 851 mitochondria. Mitochondrion. 2017;33:22-37. 852 41. Morgenstern M, Stiller SB, Lübbert P, Peikert CD, Dannenmaier S, Drepper F, et al. 853 Definition of a High-Confidence Mitochondrial Proteome at Quantitative Scale. Cell reports. 854 2017;19(13):2836-52. 855 42. Putignani L, Tait A, Smith HV, Horner D, Tovar J, Tetley L, et al. Characterization of a 856 mitochondrion-like organelle in Cryptosporidium parvum. Parasitology. 2004;129(Pt 1):1-18. 857 43. Pryszcz LP, Huerta-Cepas J, Gabaldón T. MetaPhOrs: orthology and paralogy 858 predictions from multiple phylogenetic evidence using a consistency-based confidence 859 score. Nucleic acids research. 2011;39(5):e32. 860 44. Bender A, van Dooren GG, Ralph SA, McFadden GI, Schneider G. Properties and 861 prediction of mitochondrial transit peptides from Plasmodium falciparum. Molecular and 862 biochemical parasitology. 2003;132(2):59-66. 863

    .CC-BY-NC 4.0 International licenseperpetuity. It is made available under apreprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in

    The copyright holder for thisthis version posted January 23, 2021. ; https://doi.org/10.1101/2021.01.22.427784doi: bioRxiv preprint

    https://doi.org/10.1101/2021.01.22.427784http://creativecommons.org/licenses/by-nc/4.0/

  • 23

    45. Alberts BJ, A.; Lewis, J.; Raff, M.; Roberts, K.; Walter, P. Molecular Biology of the Cell 864 New York: Garland Science; 2002 [4th edition:[The Mitochondrion]. Available from: 865 https://www.ncbi.nlm.nih.gov/books/NBK26894/. 866 46. Kozlowski LP. Proteome-pI: proteome isoelectric point database. Nucleic acids 867 research. 2017;45(D1):D1112-d6. 868 47. Patrickios CS. Polypeptide Amino Acid Composition and Isoelectric Point: 1. A Closed-869 Form Approximation. Journal of Colloid and Interface Science. 1995;175(1):256-60. 870 48. Otto TD, Böhme U, Jackson AP, Hunt M, Franke-Fayard B, Hoeijmakers WA, et al. A 871 comprehensive evaluation of rodent malaria parasite genomes and gene expression. BMC 872 biology. 2014;12:86. 873 49. Matz JM, Kooij TW. Towards genome-wide experimental genetics in the in vivo 874 malaria model parasite Plasmodium berghei. Pathogens and global health. 2015;109(2):46-875 60. 876 50. Deligianni E, Morgan RN, Bertuccini L, Kooij TW, Laforge A, Nahar C, et al. Critical role 877 for a stage-specific actin in male exflagellation of the malaria parasite. Cellular microbiology. 878 2011;13(11):1714-30. 879 51. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an 880 open-source platform for biological-image analysis. Nature methods. 2012;9(7):676-82. 881 52. R Core Team. R: A Language and Environment for Statistical Computing. Vienna, 882 Austria: R Foundation for Statistical Computing; 2015. 883 53. Warnes GR, Bolker B, Bonebakker L, Gentleman R, Liaw WHA, Lumley T, et al. gplots: 884 Various R Programming Tools for Plotting Data. 2016. 885 54. Wickham H. ggplot2: Elegant Graphics for Data Analysis. Springer-Verlag New York; 886 2016. 887 55. Sing T, Sander O, Beerenwinkel N, Lengauer T. ROCR: visualizing classifier 888 performance in R. Bioinformatics (Oxford, England). 2005;21(20):3940-1. 889 56. Wickham H. scales: Scale Functions for Visualization. 2017. 890 57. Wickham H. Reshaping data with the reshape package. Journal of Statistical 891 Software. 2007;21(12). 892 58. Takeda K, Komuro Y, Hayakawa T, Oguchi H, Ishida Y, Murakami S, et al. 893 Mitochondrial phosphoglycerate mutase 5 uses alternate catalytic activity as a protein 894 serine/threonine phosphatase to activate ASK1. Proceedings of the National Academy of 895 Sciences of the United States of America. 2009;106(30):12301-5. 896 59. Lo SC, Hannink M. PGAM5 tethers a ternary complex containing Keap1 and Nrf2 to 897 mitochondria. Experimental cell research. 2008;314(8):1789-803. 898 60. Ma K, Chen G, Li W, Kepp O, Zhu Y, Chen Q. Mitophagy, Mitochondrial Homeostasis, 899 and Cell Fate. Frontiers in cell and developmental biology. 2020;8:467. 900 61. Lo SC, Hannink M. PGAM5, a Bcl-XL-interacting protein, is a novel substrate for the 901 redox-regulated Keap1-dependent ubiquitin ligase complex. The Journal of biological 902 chemistry. 2006;281(49):37893-903. 903 62. Krogh A, Larsson B, von Heijne G, Sonnhammer EL. Predicting transmembrane 904 protein topology with a hidden Markov model: application to complete genomes. Journal of 905 molecular biology. 2001;305(3):567-80. 906 63. Sidik SM, Huet D, Ganesan SM, Huynh MH, Wang T, Nasamu AS, et al. A Genome-907 wide CRISPR Screen in Toxoplasma Identifies Essential Apicomplexan Genes. Cell. 908 2016;166(6):1423-35.e12. 909

    .CC-BY-NC 4.0 International licenseperpetuity. It is made available under apreprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in

    The copyright holder for thisthis version posted January 23, 2021. ; https://doi.org/10.1101/2021.01.22.427784doi: bioRxiv preprint

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  • 24

    64. Ude S, Lassak J, Starosta AL, Kraxenberger T, Wilson DN, Jung K. Translation 910 elongation factor EF-P alleviates ribosome stalling at polyproline stretches. Science (New 911 York, NY). 2013;339(6115):82-5. 912 65. Yanagisawa T, Sumida T, Ishii R, Takemoto C, Yokoyama S. A paralog of lysyl-tRNA 913 synthetase aminoacylates a conserved lysine residue in translation elongation factor P. 914 Nature structural & molecular biology. 2010;17(9):1136-43. 915 66. Fu X, Wang Y, Shao H, Ma J, Song X, Zhang M, et al. DegP functions as a critical 916 protease for bacterial acid resistance. The FEBS journal. 2018;285(18):3525-38. 917 67. Krojer T, Garrido-Franco M, Huber R, Ehrmann M, Clausen T. Crystal structure of 918 DegP (HtrA) reveals a new protease-chaperone machine. Nature. 2002;416(6879):455-9. 919 68. McDonough MA, Kavanagh KL, Butler D, Searls T, Oppermann U, Schofield CJ. 920 Structure of human phytanoyl-CoA 2-hydroxylase identifies molecular mechanisms of 921 Refsum disease. The Journal of biological chemistry. 2005;280(49):41101-10. 922 69. Xu Q, Rawlings ND, Chiu HJ, Jaroszewski L, Klock HE, Knuth MW, et al. Structural 923 analysis of papain-like NlpC/P60 superfamily enzymes with a circularly permuted topology 924 reveals potential lipid binding sites. PloS one. 2011;6(7):e22013. 925 70. Mary C, Scherrer A, Huck L, Lakkaraju AK, Thomas Y, Johnson AE, et al. Residues in 926 SRP9/14 essential for elongation arrest activity of the signal recognition particle define a 927 positively charged functional domain on one side of the protein. RNA (New York, NY). 928 2010;16(5):969-79. 929 71. Janda CY, Li J, Oubridge C, Hernández H, Robinson CV, Nagai K. Recognition of a 930 signal peptide by the signal recognition particle. Nature. 2010;465(7297):507-10. 931 72. Hilario E, Li Y, Niks D, Fan L. The structure of a Xanthomonas general stress protein 932 involved in citrus canker reveals its flavin-binding property. Acta crystallographica Section D, 933 Biological crystallography. 2012;68(Pt 7):846-53. 934 73. Potter SC, Luciani A, Eddy SR, Park Y, Lopez R, Finn RD. HMMER web server: 2018 935 update. Nucleic acids research. 2018;46(W1):W200-w4. 936 74. Posayapisit N, Songsungthong W, Koonyosying P, Falade MO, Uthaipibull C, 937 Yuthavong Y, et al. Cytochrome c and c1 heme lyases are essential in Plasmodium berghei. 938 Molecular and biochemical parasitology. 2016;210(1-2):32-6. 939 75. Babbitt SE, San Francisco B, Bretsnyder EC, Kranz RG. Conserved residues of the 940 human mitochondrial holocytochrome c synthase mediate interactions with heme. 941 Biochemistry. 2014;53(32):5261-71. 942 76. Wang KT, Desmolaize B, Nan J, Zhang XW, Li LF, Douthwaite S, et al. Structure of the 943 bifunctional methyltransferase YcbY (RlmKL) that adds the m7G2069 and m2G2445 944 modifications in Escherichia coli 23S rRNA. Nucleic acids research. 2012;40(11):5138-48. 945 77. Feagin JE, Harrell MI, Lee JC, Coe KJ, Sands BH, Cannone JJ, et al. The fragmented 946 mitochondrial ribosomal RNAs of Plasmodium falciparum. PloS one. 2012;7(6):e38320. 947 78. van Dam TJP, Kennedy J, van der Lee R, de Vrieze E, Wunderlich KA, Rix S, et al. 948 CiliaCarta: An integrated and validated compendium of ciliary genes. PloS one. 949 2019;14(5):e0216705. 950 79. Smith DG, Gawryluk RM, Spencer DF, Pearlman RE, Siu KW, Gray MW. Exploring the 951 mitochondrial proteome of the ciliate protozoon Tetrahymena thermophila: direct analysis 952 by tandem mass spectrometry. Journal of molecular biology. 2007;374(3):837-63. 953

    954

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