1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Microbiology
  4. Volume 77, 2023
  5. Article

Annual Review of Microbiology

Volume 77, 2023

Unique Properties of Apicomplexan Mitochondria

Abstract

Apicomplexan parasites constitute more than 6,000 species infecting a wide range of hosts. These include important pathogens such as those causing malaria and toxoplasmosis. Their evolutionary emergence coincided with the dawn of animals. Mitochondrial genomes of apicomplexan parasites have undergone dramatic reduction in their coding capacity, with genes for only three proteins and ribosomal RNA genes present in scrambled fragments originating from both strands. Different branches of the apicomplexans have undergone rearrangements of these genes, with having massive variations in gene arrangements spread over multiple copies. The vast evolutionary distance between the parasite and the host mitochondria has been exploited for the development of antiparasitic drugs, especially those used to treat malaria, wherein inhibition of the parasite mitochondrial respiratory chain is selectively targeted with little toxicity to the host mitochondria. We describe additional unique characteristics of the parasite mitochondria that are being investigated and provide greater insights into these deep-branching eukaryotic pathogens.

Keyword(s): antiparasitic drugs, ATP synthase, electron transport complexes, Myzozoa, Plasmodium, Toxoplasma
Loading

Article metrics loading...

/content/journals/10.1146/annurev-micro-032421-120540
2023-09-15
2024-04-28
Loading full text...

Full text loading...

/deliver/fulltext/micro/77/1/annurev-micro-032421-120540.html?itemId=/content/journals/10.1146/annurev-micro-032421-120540&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Abrahamsen MS, Templeton TJ, Enomoto S, Abrahante JE, Zhu G et al. 2004. Complete genome sequence of the apicomplexan, Cryptosporidium parvum. Science 304:441–45
     [Google Scholar]
  2. 2.
    Adl SM, Bass D, Lane CE, Lukes J, Schoch CL et al. 2019. Revisions to the classification, nomenclature, and diversity of eukaryotes. J. Eukaryot. Microbiol. 66:4–119
     [Google Scholar]
  3. 3.
    Adl SM, Simpson AG, Lane CE, Lukes J, Bass D et al. 2012. The revised classification of eukaryotes. J. Eukaryot. Microbiol. 59:429–93
     [Google Scholar]
  4. 4.
    Araujo FG, Huskinson J, Remington JS. 1991. Remarkable in vitro and in vivo activities of the hydroxynaphthoquinone 566C80 against tachyzoites and tissue cysts of Toxoplasma gondii. Antimicrob. Agents Chemother. 35:293–99
     [Google Scholar]
  5. 5.
    Bakshi RP, Tatham LM, Savage AC, Tripathi AK, Mlambo G et al. 2018. Long-acting injectable atovaquone nanomedicines for malaria prophylaxis. Nat. Commun. 9:315
     [Google Scholar]
  6. 6.
    Balabaskaran Nina P, Dudkina NV, Kane LA, van Eyk JE, Boekema EJ et al. 2010. Highly divergent mitochondrial ATP synthase complexes in Tetrahymena thermophila. PLOS Biol. 8:e1000418
     [Google Scholar]
  7. 7.
    Balabaskaran Nina P, Morrisey JM, Ganesan SM, Ke H, Pershing AM et al. 2011. ATP synthase complex of Plasmodium falciparum: dimeric assembly in mitochondrial membranes and resistance to genetic disruption. J. Biol. Chem. 286:41312–22
     [Google Scholar]
  8. 8.
    Baldwin J, Michnoff CH, Malmquist NA, White J, Roth MG et al. 2005. High-throughput screening for potent and selective inhibitors of plasmodium falciparum dihydroorotate dehydrogenase. J. Biol. Chem. 280:21847–53
     [Google Scholar]
  9. 9.
    Barylyuk K, Koreny L, Ke H, Butterworth S, Crook OM et al. 2020. A comprehensive subcellular atlas of the Toxoplasma proteome via hyperLOPIT provides spatial context for protein functions. Cell Host Microbe 28:752–66.e9
     [Google Scholar]
  10. 10.
    Berna L, Marquez P, Cabrera A, Greif G, Francia ME, Robello C. 2021. Reevaluation of the Toxoplasma gondii and Neospora caninum genomes reveals misassembly, karyotype differences, and chromosomal rearrangements. Genome Res. 31:823–33
     [Google Scholar]
  11. 11.
    Berna L, Rego N, Francia ME. 2021. The elusive mitochondrial genomes of Apicomplexa: Where are we now?. Front. Microbiol. 12:751775
     [Google Scholar]
  12. 12.
    Bieri P, Greber BJ, Ban N. 2018. High-resolution structures of mitochondrial ribosomes and their functional implications. Curr. Opin. Struct. Biol. 49:44–53
     [Google Scholar]
  13. 13.
    Birth D, Kao WC, Hunte C. 2014. Structural analysis of atovaquone-inhibited cytochrome bc1 complex reveals the molecular basis of antimalarial drug action. Nat. Commun. 5:4029
     [Google Scholar]
  14. 14.
    Boyer PD. 1997. The ATP synthase—a splendid molecular machine. Annu. Rev. Biochem. 66:717–49
     [Google Scholar]
  15. 15.
    Braun HP. 2021. The two roles of complex III in plants. eLife 10:e65239
     [Google Scholar]
  16. 16.
    Braun HP, Schmitz UK. 1995. Are the ‘core’ proteins of the mitochondrial bc1 complex evolutionary relics of a processing protease?. Trends Biochem. Sci. 20:171–75
     [Google Scholar]
  17. 17.
    Bushell E, Gomes AR, Sanderson T, Anar B, Girling G et al. 2017. Functional profiling of a Plasmodium genome reveals an abundance of essential genes. Cell 170:260–72.e8
     [Google Scholar]
  18. 18.
    Carlton JM, Angiuoli SV, Suh BB, Kooij TW, Pertea M et al. 2002. Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii yoelii. Nature 419:512–19
     [Google Scholar]
  19. 19.
    Chiu JE, Renard I, Pal AC, Singh P, Vydyam P et al. 2021. Effective therapy targeting cytochrome bc1 prevents Babesia erythrocytic development and protects from lethal infection. Antimicrob. Agents Chemother. 65:e0066221
     [Google Scholar]
  20. 20.
    Christiansen C, Maus D, Hoppenz E, Murillo-Leon M, Hoffmann T et al. 2022. In vitro maturation of Toxoplasma gondii bradyzoites in human myotubes and their metabolomic characterization. Nat. Commun. 13:1168
     [Google Scholar]
  21. 21.
    Christoforou A, Mulvey CM, Breckels LM, Geladaki A, Hurrell T et al. 2016. A draft map of the mouse pluripotent stem cell spatial proteome. Nat. Commun. 7:8992
     [Google Scholar]
  22. 22.
    Cobbold SA, Santos JM, Ochoa A, Perlman DH, Llinas M. 2016. Proteome-wide analysis reveals widespread lysine acetylation of major protein complexes in the malaria parasite. Sci. Rep. 6:19722
     [Google Scholar]
  23. 23.
    Danne JC, Gornik SG, Macrae JI, McConville MJ, Waller RF. 2013. Alveolate mitochondrial metabolic evolution: dinoflagellates force reassessment of the role of parasitism as a driver of change in apicomplexans. Mol. Biol. Evol. 30:123–39
     [Google Scholar]
  24. 24.
    Dass S, Mather MW, Ke H. 2020. Divergent mitochondrial ribosomes in unicellular parasitic protozoans. Trends Parasitol. 36:318–21
     [Google Scholar]
  25. 25.
    Dass S, Mather MW, Morrisey JM, Ling L, Vaidya AB, Ke H. 2022. Transcriptional changes in Plasmodium falciparum upon conditional knock down of mitochondrial ribosomal proteins RSM22 and L23. PLOS ONE 17:e0274993
     [Google Scholar]
  26. 26.
    Doggett JS, Nilsen A, Forquer I, Wegmann KW, Jones-Brando L et al. 2012. Endochin-like quinolones are highly efficacious against acute and latent experimental toxoplasmosis. PNAS 109:15936–41
     [Google Scholar]
  27. 27.
    Evers F, Cabrera-Orefice A, Elurbe DM, Kea-Te Lindert M, Boltryk SD et al. 2021. Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum. Nat. Commun. 12:3820
     [Google Scholar]
  28. 28.
    Feagin JE, Gardner MJ, Williamson DH, Wilson RJ. 1991. The putative mitochondrial genome of Plasmodium falciparum. J. Protozool. 38:243–45
     [Google Scholar]
  29. 29.
    Feagin JE, Harrell MI, Lee JC, Coe KJ, Sands BH et al. 2012. The fragmented mitochondrial ribosomal RNAs of Plasmodium falciparum. PLOS ONE 7:e38320
     [Google Scholar]
  30. 30.
    Feagin JE, Mericle BL, Werner E, Morris M. 1997. Identification of additional rRNA fragments encoded by the Plasmodium falciparum 6 kb element. Nucleic Acids Res. 25:438–46
     [Google Scholar]
  31. 31.
    Fox BA, Bzik DJ. 2002. De novo pyrimidine biosynthesis is required for virulence of Toxoplasma gondii. Nature 415:926–29
     [Google Scholar]
  32. 32.
    Fry M, Pudney M. 1992. Site of action of the antimalarial hydroxynaphthoquinone, 2-[trans-4-(4′-chlorophenyl) cyclohexyl]-3-hydroxy-1,4-naphthoquinone (566C80). Biochem. Pharmacol. 43:1545–53
     [Google Scholar]
  33. 33.
    Gakh O, Cavadini P, Isaya G. 2002. Mitochondrial processing peptidases. Biochim. Biophys. Acta Mol. Cell Res. 1592:63–77
     [Google Scholar]
  34. 34.
    Gardner MJ, Bates PA, Ling IT, Moore DJ, McCready S et al. 1988. Mitochondrial DNA of the human malarial parasite Plasmodium falciparum. Mol. Biochem. Parasitol. 31:11–17
     [Google Scholar]
  35. 35.
    Gardner MJ, Hall N, Fung E, White O, Berriman M et al. 2002. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419:498–511
     [Google Scholar]
  36. 36.
    Gillespie DE, Salazar NA, Rehkopf DH, Feagin JE. 1999. The fragmented mitochondrial ribosomal RNAs of Plasmodium falciparum have short A tails. Nucleic Acids Res. 27:2416–22
     [Google Scholar]
  37. 37.
    Gray MW. 1988. Organelle origins and ribosomal RNA. Biochem. Cell Biol. 66:325–48
     [Google Scholar]
  38. 38.
    Gray MW. 1993. Origin and evolution of organelle genomes. Curr. Opin. Genet. Dev. 3:884–90
     [Google Scholar]
  39. 39.
    Gray MW, Lang BF, Burger G. 2004. Mitochondria of protists. Annu. Rev. Genet. 38:477–524
     [Google Scholar]
  40. 40.
    Gutteridge WE, Dave D, Richards WH. 1979. Conversion of dihydroorotate to orotate in parasitic protozoa. Biochim. Biophys. Acta Gen. Subj. 582:390–401
     [Google Scholar]
  41. 41.
    Habib S, Vaishya S, Gupta K. 2016. Translation in organelles of apicomplexan parasites. Trends Parasitol. 32:939–52
     [Google Scholar]
  42. 42.
    Hayward JA, van Dooren GG. 2019. Same same, but different: uncovering unique features of the mitochondrial respiratory chain of apicomplexans. Mol. Biochem. Parasitol. 232:111204
     [Google Scholar]
  43. 43.
    Hikosaka K, Kita K, Tanabe K. 2013. Diversity of mitochondrial genome structure in the phylum Apicomplexa. Mol. Biochem. Parasitol. 188:26–33
     [Google Scholar]
  44. 44.
    Hikosaka K, Nakai Y, Watanabe Y, Tachibana S, Arisue N et al. 2011. Concatenated mitochondrial DNA of the coccidian parasite Eimeria tenella. Mitochondrion 11:273–78
     [Google Scholar]
  45. 45.
    Hikosaka K, Watanabe Y, Tsuji N, Kita K, Kishine H et al. 2010. Divergence of the mitochondrial genome structure in the apicomplexan parasites. Babesia and Theileria. Mol. Biol. Evol. 27:1107–16
     [Google Scholar]
  46. 46.
    Hollin T, Abel S, Falla A, Pasaje CFA, Bhatia A et al. 2022. Functional genomics of RAP proteins and their role in mitoribosome regulation in Plasmodium falciparum. Nat. Commun. 13:1275
     [Google Scholar]
  47. 47.
    Hollin T, Jaroszewski L, Stajich JE, Godzik A, Le Roch KG 2021. Identification and phylogenetic analysis of RNA binding domain abundant in apicomplexans or RAP proteins. Microb. Genom. 7:mgen000541
     [Google Scholar]
  48. 48.
    Huet D, Rajendran E, van Dooren GG, Lourido S. 2018. Identification of cryptic subunits from an apicomplexan ATP synthase. eLife 7:e38097
     [Google Scholar]
  49. 49.
    Janouškovec J, Paskerova GG, Miroliubova TS, Mikhailov KV, Birley T et al. 2019. Apicomplexan-like parasites are polyphyletic and widely but selectively dependent on cryptic plastid organelles. eLife 8:e49662
     [Google Scholar]
  50. 50.
    Ji YE, Mericle BL, Rehkopf DH, Anderson JD, Feagin JE. 1996. The Plasmodium falciparum 6 kb element is polycistronically transcribed. Mol. Biochem. Parasitol. 81:211–23
     [Google Scholar]
  51. 51.
    Joseph JT, Aldritt SM, Unnasch T, Puijalon O, Wirth DF. 1989. Characterization of a conserved extrachromosomal element isolated from the avian malarial parasite Plasmodium gallinaceum. Mol. Cell. Biol. 9:3621–29
     [Google Scholar]
  52. 52.
    Kairo A, Fairlamb AH, Gobright E, Nene V. 1994. A 7.1 kb linear DNA molecule of Theileria parva has scrambled rDNA sequences and open reading frames for mitochondrially encoded proteins. EMBO J. 13:898–905
     [Google Scholar]
  53. 53.
    Kamikawa R, Inagaki Y, Sako Y. 2007. Fragmentation of mitochondrial large subunit rRNA in the dinoflagellate Alexandrium catenella and the evolution of rRNA structure in alveolate mitochondria. Protist 158:239–45
     [Google Scholar]
  54. 54.
    Ke H, Dass S, Morrisey JM, Mather MW, Vaidya AB. 2018. The mitochondrial ribosomal protein L13 is critical for the structural and functional integrity of the mitochondrion in Plasmodium falciparum. J. Biol. Chem. 293:8128–37
     [Google Scholar]
  55. 55.
    Ke H, Lewis IA, Morrisey JM, McLean KJ, Ganesan SM et al. 2015. Genetic investigation of tricarboxylic acid metabolism during the Plasmodium falciparum life cycle. Cell Rep. 11:164–74
     [Google Scholar]
  56. 56.
    Keeling PJ. 2013. The number, speed, and impact of plastid endosymbioses in eukaryotic evolution. Annu. Rev. Plant. Biol. 64:583–607
     [Google Scholar]
  57. 57.
    Keeling PJ, Burki F. 2019. Progress towards the tree of eukaryotes. Curr. Biol. 29:R808–17
     [Google Scholar]
  58. 58.
    Kessl JJ, Lange BB, Merbitz-Zahradnik T, Zwicker K, Hill P et al. 2003. Molecular basis for atovaquone binding to the cytochrome bc1 complex. J. Biol. Chem. 278:31312–18
     [Google Scholar]
  59. 59.
    Klug D, Mair GR, Frischknecht F, Douglas RG. 2016. A small mitochondrial protein present in myzozoans is essential for malaria transmission. Open Biol. 6:160034
     [Google Scholar]
  60. 60.
    Kunová N, Havalová H, Ondrovičová G, Stojkovičová B, Bauer JA et al. 2022. Mitochondrial processing peptidases—structure, function and the role in human diseases. Int. J. Mol. Sci. 23:1297
     [Google Scholar]
  61. 61.
    Kwong WK, Del Campo J, Mathur V, Vermeij MJA, Keeling PJ. 2019. A widespread coral-infecting apicomplexan with chlorophyll biosynthesis genes. Nature 568:103–7
     [Google Scholar]
  62. 62.
    Kwong WK, Irwin NAT, Mathur V, Na I, Okamoto N et al. 2021. Taxonomy of the apicomplexan symbionts of coral, including Corallicolida ord. nov., reassignment of the genus Gemmocystis, and description of new species Corallicola aquarius gen. nov. sp. nov. and Anthozoaphila gnarlus gen. nov. sp. nov. J. Eukaryot. Microbiol. 68:e12852
     [Google Scholar]
  63. 63.
    Lamb IM, Rios KT, Shukla A, Ahiya AI, Morrisey J et al. 2022. Mitochondrially targeted proximity biotinylation and proteomic analysis in Plasmodium falciparum. PLOS ONE 17:e0273357
     [Google Scholar]
  64. 64.
    Lane N, Martin W. 2010. The energetics of genome complexity. Nature 467:929–34
     [Google Scholar]
  65. 65.
    Lawres LA, Garg A, Kumar V, Bruzual I, Forquer IP et al. 2016. Radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone and atovaquone. J. Exp. Med. 213:1307–18
     [Google Scholar]
  66. 66.
    Lee C, Kim KH, Cohen P. 2016. MOTS-c: a novel mitochondrial-derived peptide regulating muscle and fat metabolism. Free Radic. . Biol. Med. 100:182–87
     [Google Scholar]
  67. 67.
    Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A et al. 2015. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 21:443–54
     [Google Scholar]
  68. 68.
    Li J, Maga JA, Cermakian N, Cedergren R, Feagin JE. 2001. Identification and characterization of a Plasmodium falciparum RNA polymerase gene with similarity to mitochondrial RNA polymerases. Mol. Biochem. Parasitol. 113:261–69
     [Google Scholar]
  69. 69.
    Lin RQ, Qiu LL, Liu GH, Wu XY, Weng YB et al. 2011. Characterization of the complete mitochondrial genomes of five Eimeria species from domestic chickens. Gene 480:28–33
     [Google Scholar]
  70. 70.
    Ling L, Mulaka M, Munro J, Dass S, Mather MW et al. 2020. Genetic ablation of the mitoribosome in the malaria parasite Plasmodium falciparum sensitizes it to antimalarials that target mitochondrial functions. J. Biol. Chem. 295:7235–48
     [Google Scholar]
  71. 71.
    Liu GH, Hou J, Weng YB, Song HQ, Li S et al. 2012. The complete mitochondrial genome sequence of Eimeria mitis (Apicomplexa: Coccidia). Mitochondrial DNA 23:341–43
     [Google Scholar]
  72. 72.
    Liu GH, Tian SQ, Cui P, Fang SF, Wang CR, Zhu XQ. 2015. The complete mitochondrial genomes of five Eimeria species infecting domestic rabbits. Exp. Parasitol. 159:67–71
     [Google Scholar]
  73. 73.
    Liu S, Roellig DM, Guo Y, Li N, Frace MA et al. 2016. Evolution of mitosome metabolism and invasion-related proteins in Cryptosporidium. BMC Genom. 17:1006
     [Google Scholar]
  74. 74.
    Llanos-Cuentas A, Casapia M, Chuquiyauri R, Hinojosa JC, Kerr N et al. 2018. Antimalarial activity of single-dose DSM265, a novel plasmodium dihydroorotate dehydrogenase inhibitor, in patients with uncomplicated Plasmodium falciparum or Plasmodium vivax malaria infection: a proof-of-concept, open-label, phase 2A study. Lancet Infect. Dis. 18:874–83
     [Google Scholar]
  75. 75.
    Looareesuwan S, Chulay JD, Canfield CJ, Hutchinson DB. 1999. Malarone (atovaquone and proguanil hydrochloride): a review of its clinical development for treatment of malaria. Malarone Clinical Trials Study Group. Am. J. Trop. Med. Hyg. 60:533–41
     [Google Scholar]
  76. 76.
    Looareesuwan S, Viravan C, Webster HK, Kyle DE, Hutchinson DB, Canfield CJ. 1996. Clinical studies of atovaquone, alone or in combination with other antimalarial drugs, for treatment of acute uncomplicated malaria in Thailand. Am. J. Trop. Med. Hyg. 54:62–66
     [Google Scholar]
  77. 77.
    Looareesuwan S, Wilairatana P, Glanarongran R, Indravijit KA, Supeeranontha L et al. 1999. Atovaquone and proguanil hydrochloride followed by primaquine for treatment of Plasmodium vivax malaria in Thailand. Trans. R. Soc. Trop. Med. Hyg. 93:637–40
     [Google Scholar]
  78. 78.
    Maclean AE, Bridges HR, Silva MF, Ding S, Ovciarikova J et al. 2021. Complexome profile of Toxoplasma gondii mitochondria identifies divergent subunits of respiratory chain complexes including new subunits of cytochrome bc1 complex. PLOS Pathog. 17:e1009301
     [Google Scholar]
  79. 79.
    Maclean AE, Hayward JA, Huet D, van Dooren GG, Sheiner L. 2022. The mystery of massive mitochondrial complexes: the apicomplexan respiratory chain. Trends Parasitol. 38:1041–52
     [Google Scholar]
  80. 80.
    MacRae JI, Dixon MW, Dearnley MK, Chua HH, Chambers JM et al. 2013. Mitochondrial metabolism of sexual and asexual blood stages of the malaria parasite Plasmodium falciparum. BMC Biol. 11:67
     [Google Scholar]
  81. 81.
    MacRae JI, Sheiner L, Nahid A, Tonkin C, Striepen B, McConville MJ. 2012. Mitochondrial metabolism of glucose and glutamine is required for intracellular growth of Toxoplasma gondii. Cell Host Microbe 12:682–92
     [Google Scholar]
  82. 82.
    Martin W, Muller M. 1998. The hydrogen hypothesis for the first eukaryote. Nature 392:37–41
     [Google Scholar]
  83. 83.
    Mather MW, Darrouzet E, Valkova-Valchanova M, Cooley JW, McIntosh MT et al. 2005. Uncovering the molecular mode of action of the antimalarial drug atovaquone using a bacterial system. J. Biol. Chem. 280:27458–65
     [Google Scholar]
  84. 84.
    Mather MW, Henry KW, Vaidya AB. 2007. Mitochondrial drug targets in apicomplexan parasites. Curr. Drug Targets 8:49–60
     [Google Scholar]
  85. 85.
    Mather MW, Vaidya AB. 2008. Mitochondria in malaria and related parasites: ancient, diverse and streamlined. J. Bioenerg. Biomembr. 40:425–33
     [Google Scholar]
  86. 86.
    Mathur V, Wakeman KC, Keeling PJ. 2021. Parallel functional reduction in the mitochondria of apicomplexan parasites. Curr. Biol. 31:2920–28.e4
     [Google Scholar]
  87. 87.
    McFadden DC, Tomavo S, Berry EA, Boothroyd JC. 2000. Characterization of cytochrome b from Toxoplasma gondii and Qo domain mutations as a mechanism of atovaquone-resistance. Mol. Biochem. Parasitol. 108:1–12
     [Google Scholar]
  88. 88.
    McIntosh MT, Srivastava R, Vaidya AB. 1998. Divergent evolutionary constraints on mitochondrial and nuclear genomes of malaria parasites. Mol. Biochem. Parasitol. 95:69–80
     [Google Scholar]
  89. 89.
    Miley GP, Pou S, Winter R, Nilsen A, Li Y et al. 2015. ELQ-300 prodrugs for enhanced delivery and single-dose cure of malaria. Antimicrob. Agents Chemother. 59:5555–60
     [Google Scholar]
  90. 90.
    Miller B, Kim SJ, Kumagai H, Yen K, Cohen P. 2022. Mitochondria-derived peptides in aging and healthspan. J. Clin. Investig. 132:e158449
     [Google Scholar]
  91. 91.
    Mogi T, Kita K. 2009. Identification of mitochondrial Complex II subunits SDH3 and SDH4 and ATP synthase subunits a and b in Plasmodium spp. Mitochondrion 9:443–53
     [Google Scholar]
  92. 92.
    Mohring F, Rahbari M, Zechmann B, Rahlfs S, Przyborski JM et al. 2017. Determination of glutathione redox potential and pH value in subcellular compartments of malaria parasites. Free Radic. . Biol. Med. 104:104–17
     [Google Scholar]
  93. 93.
    Morales J, Mogi T, Mineki S, Takashima E, Mineki R et al. 2009. Novel mitochondrial complex II isolated from Trypanosoma cruzi is composed of 12 peptides including a heterodimeric Ip subunit. J. Biol. Chem. 284:7255–63
     [Google Scholar]
  94. 94.
    Muhleip A, Kock Flygaard R, Ovciarikova J, Lacombe A, Fernandes P et al. 2021. ATP synthase hexamer assemblies shape cristae of Toxoplasma mitochondria. Nat. Commun. 12:120
     [Google Scholar]
  95. 95.
    Mulvey CM, Breckels LM, Geladaki A, Britovsek NK, Nightingale DJH et al. 2017. Using hyperLOPIT to perform high-resolution mapping of the spatial proteome. Nat. Protoc. 12:1110–35
     [Google Scholar]
  96. 96.
    Namasivayam S, Baptista RP, Xiao W, Hall EM, Doggett JS et al. 2021. A novel fragmented mitochondrial genome in the protist pathogen Toxoplasma gondii and related tissue coccidia. Genome Res. 31:852–65
     [Google Scholar]
  97. 97.
    Nene V, Morzaria S, Bishop R. 1998. Organisation and informational content of the Theileria parva genome. Mol. Biochem. Parasitol. 95:1–8
     [Google Scholar]
  98. 98.
    Nilsen A, LaCrue AN, White KL, Forquer IP, Cross RM et al. 2013. Quinolone-3-diarylethers: a new class of antimalarial drug. Sci. Transl. Med. 5:177ra37
     [Google Scholar]
  99. 99.
    Obornik M, Janouškovec J, Chrudimsky T, Lukes J. 2009. Evolution of the apicoplast and its hosts: from heterotrophy to autotrophy and back again. Int. J. Parasitol. 39:1–12
     [Google Scholar]
  100. 100.
    Oppenheim RD, Creek DJ, Macrae JI, Modrzynska KK, Pino P et al. 2014. BCKDH: the missing link in apicomplexan mitochondrial metabolism is required for full virulence of Toxoplasma gondii and Plasmodium berghei. PLOS Pathog. 10:e1004263
     [Google Scholar]
  101. 101.
    Ossorio PN, Sibley LD, Boothroyd JC. 1991. Mitochondrial-like DNA sequences flanked by direct and inverted repeats in the nuclear genome of Toxoplasma gondii. J. Mol. Biol. 222:525–36
     [Google Scholar]
  102. 102.
    Painter HJ, Morrisey JM, Mather MW, Vaidya AB. 2007. Specific role of mitochondrial electron transport in blood-stage Plasmodium falciparum. Nature 446:88–91
     [Google Scholar]
  103. 103.
    Pamukcu S, Cerutti A, Bordat Y, Hem S, Rofidal V, Besteiro S. 2021. Differential contribution of two organelles of endosymbiotic origin to iron-sulfur cluster synthesis and overall fitness in Toxoplasma. PLOS Pathog. 17:e1010096
     [Google Scholar]
  104. 104.
    Phillips MA, Lotharius J, Marsh K, White J, Dayan A et al. 2015. A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria. Sci. Transl. Med. 7:296ra111
     [Google Scholar]
  105. 105.
    Preiser PR, Wilson RJ, Moore PW, McCready S, Hajibagheri MA et al. 1996. Recombination associated with replication of malarial mitochondrial DNA. EMBO J. 15:684–93
     [Google Scholar]
  106. 106.
    Ramrath DJF, Niemann M, Leibundgut M, Bieri P, Prange C et al. 2018. Evolutionary shift toward protein-based architecture in trypanosomal mitochondrial ribosomes. Science 362:eaau7735
     [Google Scholar]
  107. 107.
    Rudashevskaya EL, Sickmann A, Markoutsa S. 2016. Global profiling of protein complexes: current approaches and their perspective in biomedical research. Expert Rev. Proteom. 13:951–64
     [Google Scholar]
  108. 108.
    Salunke R, Mourier T, Banerjee M, Pain A, Shanmugam D. 2018. Highly diverged novel subunit composition of apicomplexan F-type ATP synthase identified from Toxoplasma gondii. PLOS Biol. 16:e2006128
     [Google Scholar]
  109. 109.
    Schagger H, Pfeiffer K. 2000. Supercomplexes in the respiratory chains of yeast and mammalian mitochondria. EMBO J. 19:1777–83
     [Google Scholar]
  110. 110.
    Schilling B, Murray J, Yoo CB, Row RH, Cusack MP et al. 2006. Proteomic analysis of succinate dehydrogenase and ubiquinol-cytochrome c reductase (Complex II and III) isolated by immunoprecipitation from bovine and mouse heart mitochondria. Biochim. Biophys. Acta Mol. Basis Dis. 1762:213–22
     [Google Scholar]
  111. 111.
    Seidi A, Muellner-Wong LS, Rajendran E, Tjhin ET, Dagley LF et al. 2018. Elucidating the mitochondrial proteome of Toxoplasma gondii reveals the presence of a divergent cytochrome c oxidase. eLife 7:e38131
     [Google Scholar]
  112. 112.
    Sherman IW. 1979. Biochemistry of Plasmodium (malarial parasites). Microbiol. Rev. 43:453–95
     [Google Scholar]
  113. 113.
    Shikha S, Silva MF, Sheiner L. 2022. Identification and validation of Toxoplasma gondii mitoribosomal large subunit components. Microorganisms 10:863
     [Google Scholar]
  114. 114.
    Smilkstein MJ, Pou S, Krollenbrock A, Bleyle LA, Dodean RA et al. 2019. ELQ-331 as a prototype for extremely durable chemoprotection against malaria. Malar. J. 18:291
     [Google Scholar]
  115. 115.
    Srivastava IK, Morrisey JM, Darrouzet E, Daldal F, Vaidya AB. 1999. Resistance mutations reveal the atovaquone-binding domain of cytochrome b in malaria parasites. Mol. Microbiol. 33:704–11
     [Google Scholar]
  116. 116.
    Srivastava IK, Rottenberg H, Vaidya AB. 1997. Atovaquone, a broad spectrum antiparasitic drug, collapses mitochondrial membrane potential in a malarial parasite. J. Biol. Chem. 272:3961–66
     [Google Scholar]
  117. 117.
    Srivastava IK, Vaidya AB. 1999. A mechanism for the synergistic antimalarial action of atovaquone and proguanil. Antimicrob. Agents Chemother. 43:1334–39
     [Google Scholar]
  118. 118.
    Stickles AM, de Almeida MJ, Morrisey JM, Sheridan KA, Forquer IP et al. 2015. Subtle changes in endochin-like quinolone structure alter the site of inhibition within the cytochrome bc1 complex of Plasmodium falciparum. Antimicrob. Agents Chemother. 59:1977–82
     [Google Scholar]
  119. 119.
    Stickles AM, Smilkstein MJ, Morrisey JM, Li Y, Forquer IP et al. 2016. Atovaquone and ELQ-300 combination therapy as a novel dual-site cytochrome bc1 inhibition strategy for malaria. Antimicrob. Agents Chemother. 60:4853–59
     [Google Scholar]
  120. 120.
    Suplick K, Morrisey J, Vaidya AB. 1990. Complex transcription from the extrachromosomal DNA encoding mitochondrial functions of Plasmodium yoelii. Mol. Cell Biol. 10:6381–88
     [Google Scholar]
  121. 121.
    Takeo S, Kokaze A, Ng CS, Mizuchi D, Watanabe JI et al. 2000. Succinate dehydrogenase in Plasmodium falciparum mitochondria: molecular characterization of the SDHA and SDHB genes for the catalytic subunits, the flavoprotein (Fp) and iron-sulfur (Ip) subunits. Mol. Biochem. Parasitol. 107:191–205
     [Google Scholar]
  122. 122.
    Tanaka TQ, Hirai M, Watanabe Y, Kita K. 2012. Toward understanding the role of mitochondrial complex II in the intraerythrocytic stages of Plasmodium falciparum: gene targeting of the Fp subunit. Parasitol. Int. 61:726–28
     [Google Scholar]
  123. 123.
    Tobiasson V, Amunts A. 2020. Ciliate mitoribosome illuminates evolutionary steps of mitochondrial translation. eLife 9:e59264
     [Google Scholar]
  124. 124.
    Usey MM, Huet D. 2022. Parasite powerhouse: a review of the Toxoplasma gondii mitochondrion. J. Eukaryot. Microbiol. 69:e12906
     [Google Scholar]
  125. 125.
    Vaidya AB, Akella R, Suplick K. 1989. Sequences similar to genes for two mitochondrial proteins and portions of ribosomal RNA in tandemly arrayed 6-kilobase-pair DNA of a malarial parasite. Mol. Biochem. Parasitol. 35:97–107
     [Google Scholar]
  126. 126.
    Vaidya AB, Arasu P. 1987. Tandemly arranged gene clusters of malarial parasites that are highly conserved and transcribed. Mol. Biochem. Parasitol. 22:249–57
     [Google Scholar]
  127. 127.
    Vaidya AB, Lashgari MS, Pologe LG, Morrisey J. 1993. Structural features of Plasmodium cytochrome b that may underlie susceptibility to 8-aminoquinolines and hydroxynaphthoquinones. Mol. Biochem. Parasitol. 58:33–42
     [Google Scholar]
  128. 128.
    Vaidya AB, Mather MW. 2009. Mitochondrial evolution and functions in malaria parasites. Annu. Rev. Microbiol. 63:249–67
     [Google Scholar]
  129. 129.
    van Dooren GG, Striepen B. 2013. The algal past and parasite present of the apicoplast. Annu. Rev. Microbiol. 67:271–89
     [Google Scholar]
  130. 130.
    Walker JE. 1994. The regulation of catalysis in ATP synthase. Curr. Opin. Struct. Biol. 4:912–18
     [Google Scholar]
  131. 131.
    Waller RF, Keeling PJ. 2006. Alveolate and chlorophycean mitochondrial cox2 genes split twice independently. Gene 383:33–37
     [Google Scholar]
  132. 132.
    Waltz F, Salinas-Giege T, Englmeier R, Meichel H, Soufari H et al. 2021. How to build a ribosome from RNA fragments in Chlamydomonas mitochondria. Nat. Commun. 12:7176
     [Google Scholar]
  133. 133.
    White J, Dhingra SK, Deng X, El Mazouni F, Lee MCS et al. 2019. Identification and mechanistic understanding of dihydroorotate dehydrogenase point mutations in Plasmodium falciparum that confer in vitro resistance to the clinical candidate DSM265. ACS Infect. Dis. 5:90–101
     [Google Scholar]
  134. 134.
    Williamson DH, Preiser PR, Wilson RJ. 1996. Organelle DNAs: the bit players in malaria parasite DNA replication. Parasitol. Today 12:357–62
     [Google Scholar]
  135. 135.
    Williamson DH, Wilson RJ, Bates PA, McCready S, Perler F, Qiang BU. 1985. Nuclear and mitochondrial DNA of the primate malarial parasite Plasmodium knowlesi. Mol. Biochem. Parasitol. 14:199–209
     [Google Scholar]
  136. 136.
    Wittig I, Braun HP, Schagger H. 2006. Blue native PAGE. Nat. Protoc. 1:418–28
     [Google Scholar]
  137. 137.
    Xia D, Yu CA, Kim H, Xia JZ, Kachurin AM et al. 1997. Crystal structure of the cytochrome bc1 complex from bovine heart mitochondria. Science 277:60–66
     [Google Scholar]
  138. 138.
    Xu P, Widmer G, Wang Y, Ozaki LS, Alves JM et al. 2004. The genome of Cryptosporidium hominis. Nature 431:1107–12
     [Google Scholar]
  139. 139.
    Yoon TK, Lee CH, Kwon O, Kim MS. 2022. Exercise, mitohormesis, and mitochondrial ORF of the 12S rRNA type C (MOTS-c). Diabetes Metab. J. 46:402–13
     [Google Scholar]
/content/journals/10.1146/annurev-micro-032421-120540
Loading
Unique Properties of Apicomplexan Mitochondria
Annual Review of Microbiology 77, 541 (2023); https://doi.org/10.1146/annurev-micro-032421-120540
/content/journals/10.1146/annurev-micro-032421-120540
/content/journals/10.1146/annurev-micro-032421-120540
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error