Programmed Cell Death in Protists without Mitochondria: The Missing Link

Part of the Molecular Biology Intelligence Unit book series (MBIU)


Programmed cell death (PCD), a fundamental process that can be triggered in all cells, was supposed until recently solely centred on the mitochondrion. However, in amitochondriate organisms where only hydrogenosomes and mitosomes subsist as mitochondria relics, recent findings show that PCD still occurs. This exciting discovery is presented here in the light of the development of sequencing project in various different species as well as recent findings about mitochondrial derivates and ancestral viruses, contributing to a better understanding of the life tree as well as to the future discovery of new molecules of interest.


Programme Cell Death Unicellular Organism Programme Cell Death Process Cell Death Diff Life Tree 
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  1. 1.
    Kasting JF, Siefert JL. Life and the evolution of earth’s atmosphere. Science 2002; 296:1066–1068.PubMedCrossRefGoogle Scholar
  2. 2.
    Newman DK, Banfield JF. Geomicrobiology: how molecular-scale interactions underpin biogeochemical systems. Science 2002; 296:1071–1077.PubMedCrossRefGoogle Scholar
  3. 3.
    Carroll SB. Chance and necessity: the evolution of morphological complexity, and diversity. Nature 2001; 409:1102–1109.PubMedCrossRefGoogle Scholar
  4. 4.
    Nisbet EG, Sleep NH. The habitat and nature of early life. Nature 2001; 409:1083–1091.PubMedCrossRefGoogle Scholar
  5. 5.
    Alberts B. The Cell as a Collection Overview of Protein Machines: Preparing the Next Generation of Molecular Biologists. Cell 1998; 92:291–294.PubMedCrossRefGoogle Scholar
  6. 6.
    Cavalier-Smith T, Brasier M, Embley TM. Introduction: how and when did microbes change the world? Phil Trans R Soc B 2006; 361:845–850.PubMedCrossRefGoogle Scholar
  7. 7.
    Baldauf SL. The Deep Roots of Eukaryotes. Science 2003; 300:1703–1706.PubMedCrossRefGoogle Scholar
  8. 8.
    Klobutcher LA, Farabaugh PJ. Shifty ciliates: frequent programmed translational frameshifting in Euplotids. Cell 2002; 111:763–766.PubMedCrossRefGoogle Scholar
  9. 9.
    Moreno Diaz de la Espina S, Alverca E, Cuadradoc A et al. Organization of the genome and gene expression in a nuclear environment lacking histones and nucleosomes: the amazing dinoflagellates. Eur J Cell Biol 2005; 284:137–149.CrossRefGoogle Scholar
  10. 10.
    Schopf JW. Fossil evidence of Archaean life. Phil Trans R Soc B 2006; 361:869–885.PubMedCrossRefGoogle Scholar
  11. 11.
    Zimmer C. How and Where Did Life on Earth Arise? Science 2005; 309:89.PubMedCrossRefGoogle Scholar
  12. 12.
    Rees DC, Howard JB. The Interface Between the Biological and Inorganic Worlds: Iron-Sulfur Metalloclusters. Science 2003; 300:929–930.PubMedCrossRefGoogle Scholar
  13. 13.
    Embley TM, Martin W. Eukaryotic evolution, changes and challenges. Nature 2006; 440:623–630.PubMedCrossRefGoogle Scholar
  14. 14.
    Cavalier-Smith T-Cell evolution and Earth history: stasis and revolution. Phil Trans R Soc B 2006; 361:969–1006.PubMedCrossRefGoogle Scholar
  15. 15.
    Martin W, Martin Embley T. Early evolution comes full circle. Nature 2004; 431:134–136.PubMedCrossRefGoogle Scholar
  16. 16.
    Forterre P. The origin of DNA genomes and DNA replication proteins. Curr Opin Microbiol 2002; 5:525–532.PubMedCrossRefGoogle Scholar
  17. 17.
    Woose CR, Kandler O, Wheelis ML. Towards a natural system of organisms: Proposal for the domains Archaea, Bacteria, and Eucarya. Proc Natl Acad Sci USA 1990; 87:4576–4579.CrossRefGoogle Scholar
  18. 18.
    Dyall SD, Brown MT, Johnson PJ. Ancient invasions: from endosymbionts to organelles. Science 2004; 304:253–257.PubMedCrossRefGoogle Scholar
  19. 19.
    Rivera MC, Lake JA. The ring of life provides evidence for a genome fusion origin of eukaryotes. Nature 2004; 431:152–155.PubMedCrossRefGoogle Scholar
  20. 20.
    Forterre P. The origin of viruses and their possible roles in major evolutionary transitions. Virus Res 2006; 117:5–16.PubMedCrossRefGoogle Scholar
  21. 21.
    Genetello C, Van Larebeke N, Holsters M et al. Ti plasmids of Agrobacterium as conjugative plasmids. Nature 1977; 26:561–563.CrossRefGoogle Scholar
  22. 22.
    Philippe H, Lopez P, Brinkmann et al. Early-branching or fast-evolving eukaryotes? An answer based on slowly evolving positions. Proc R Soc Lond B 2000; 267:1213–1221.CrossRefGoogle Scholar
  23. 23.
    Richards TA, Cavalier-Smith T. Myosin domain evolution and the primary divergence of eukaryotes. Nature 2005; 436:1113–1118.PubMedCrossRefGoogle Scholar
  24. 24.
    van der Giezen M, Tovar J, Clark CG. Mitochondrion-derived organelles in protists and fungi. Int Rev Cytol 2005; 244:175–225.PubMedCrossRefGoogle Scholar
  25. 25.
    Embley TM, Hirt RP. Early branching eukaryotes? Curr Opin Genet Dev 1998; 8:624–629.PubMedCrossRefGoogle Scholar
  26. 26.
    Tovar J, Fischer A, Graham Clark C. The mitosome, a novel organelle related to mitochondria in the amitochondrial parasite Entamoeba histolytica. Mol Microb 1999; 32:1013–1021.CrossRefGoogle Scholar
  27. 27.
    Liu J, Glazko G, Mushegian A. Protein repertoire of double-stranded DNA bacteriophages. Virus Res 2006; 117:68–80.PubMedCrossRefGoogle Scholar
  28. 28.
    Burnett RM. More barrels from the viral tree of life. Proc Nat, Acad Sci USA 2006; 103:3–4.CrossRefGoogle Scholar
  29. 29.
    Bamford DH. Evolution of Viral Structure. Theor Pop Biol 2002; 61:461–470.CrossRefGoogle Scholar
  30. 30.
    Suzan-Monti M, La Scola B, Raoult D. Genomic and evolutionary aspects of Mimivirus. Virus Res 2006; 117:145–155.PubMedCrossRefGoogle Scholar
  31. 31.
    Iyer LM, Balaji S, Koonin EV et al. Evolutionary genomics of nucleo-cytoplasic, large DNA viruses. Virus Res 2006; 117:156–184.PubMedCrossRefGoogle Scholar
  32. 32.
    Tielens AG, Rotte C, van Hellemon JJ et al. Mitochondria as we don’t know them. Trends Biochem Sci 2002; 27:564–572.PubMedCrossRefGoogle Scholar
  33. 33.
    Pfanner N, Geissler A. Versatility of the mitochondrial protein import machinery. Nat Rev Mol Cell Biol 2001; 2:339–349.PubMedCrossRefGoogle Scholar
  34. 34.
    Gray MW, Lang F, Burger G. Mitochondria of the protists. Annu Rev Genet 2004; 38:477–524.PubMedCrossRefGoogle Scholar
  35. 35.
    Newmeyer DD, Ferguson-Miller S. Mitochondria: releasing power for life and unleashing the machineries of death. Cell 2003; 112:481–490.PubMedCrossRefGoogle Scholar
  36. 36.
    Boxma B, de Graaf RM, van der Staay GW et al. An anaerobic mitochondrion that produces hydrogen. Nature 2005; 434:74–79.PubMedCrossRefGoogle Scholar
  37. 37.
    Nasirudeen AM, Tan KS. Isolation and characterization of the mitochondrion-like organelle from Blastocystis hominis. J Micro Methods 2004; 58:101–109.CrossRefGoogle Scholar
  38. 38.
    Muller M. The hydrogenosome. J Gen Microbiol 1993; 139:2879–2889.PubMedGoogle Scholar
  39. 39.
    Embley TM, van der Giezen M, Horner DS et al. Hydrogenosomes, mitochondria and early eukaryotic evolution. IUBMB Life 2003; 55:387–95.PubMedCrossRefGoogle Scholar
  40. 40.
    Dyall SD, Johnson PJ. Origins of hydrogenosomes and mitochondria: Evolution and organelle biogenesis. Curr Opin Microbiol 2000; 3:404–411.PubMedCrossRefGoogle Scholar
  41. 41.
    Dyall SD, Koehler CM, Delgadillo-Correa MG et al. Presence of a member of the mitochondrial carrier family in hydrogenosomes: Conservation of membrane-targeting pathways between hydrogenosomes and mitochondria. Mol Cell Biol 2001; 20:2488–2497.CrossRefGoogle Scholar
  42. 42.
    Mai Z, Ghosh S, Frisardi M et al. Hsp60 Is Targeted to a Cryptic Mitochondrion-Derived Organelle (“Crypton”) in the Microacrophilic Protozoan Parasite Entamoeba histolytica. Mol Cell Biol 1999; 19:2198–2205.PubMedGoogle Scholar
  43. 43.
    Ghosh S, Field J, Rogers R et al. The Entamoeba histolytica mitochondrion-derived organelle (crypton) contains double-stranded DNA and appears to be bound by a double membrane. Infect Immun 2000; 68:4319–4322.PubMedCrossRefGoogle Scholar
  44. 44.
    Williams BAP, Hirt RP, Lucocq J et al. A mitochondrial remnant in the microsporidian Trachipleistophora hominis. Nature 2002; 418:865–869.PubMedCrossRefGoogle Scholar
  45. 45.
    Putignani L, Tait A, Smith HV et al. Characterization of a mitochondrion-like organelle in Cryptosporidium parvum. Parasitology 2004; 129:1–18.PubMedCrossRefGoogle Scholar
  46. 46.
    Katinka MD, Dupra S, Cornillot E et al. Genome sequence and gene compaction of the eukaryote parasite Encephalitozoon cuniculi. Nature 2001; 414:450–453.PubMedCrossRefGoogle Scholar
  47. 47.
    Vivares C, Gouy M, Thomarat F et al. Functional and evolutionary analysis of a eukaryotic parasitic genome. Curr Opin Microbiol 2002; 5:499–505.PubMedCrossRefGoogle Scholar
  48. 48.
    Lloyd D, Harris JC. Giardia: Highly evolved parasite or early branching eukaryote? Trends Microbiol 2002; 10:122–127.PubMedCrossRefGoogle Scholar
  49. 49.
    Melino G, Knight RA, Nicotera P. How many ways to die? How many different models of cell death? Cell Death Diff 2005; 12:1457–1462.CrossRefGoogle Scholar
  50. 50.
    Ameisen JC. On the origin, evolution, and nature of programmed cell death: a timeline of four billion years. Cell Death Diff 2002; 9:367–393.CrossRefGoogle Scholar
  51. 51.
    André N. Hippocrates of Cos and apoptosis. The Lancet 2003; 361:1306.Google Scholar
  52. 52.
    Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972; 26:239–257.PubMedGoogle Scholar
  53. 53.
    Yan N, Shi Y. Mechanisms of apoptosis through structural biology. Annu Rev Cell Dev Biol 2005; 21:35–56.PubMedCrossRefGoogle Scholar
  54. 54.
    Bidère N, Su HC, Lenardo MJ. Genetic disorders of programmed cell death in the immune system. Annu Rev Immunol 2006; 24:321–52.PubMedCrossRefGoogle Scholar
  55. 55.
    Martins LM. The serine protease Omi/HttA2: a second mammalian protein with a Reaper-like function. Cell Death Diff 2002; 9:699–701.CrossRefGoogle Scholar
  56. 56.
    Faccio L, Fusco C, Chen A et al. Characterization of a novel human serine protease that has extensive homology to bacterial heat shock endoprotease HtrA and is regulated by kidney ischemia. J Biol Chem 2000; 275:2581–2582.PubMedCrossRefGoogle Scholar
  57. 57.
    Danial NN, Korsmeyer SJ. Cell Death: Critical Control Points. Cell 2004; 116:205–219.PubMedCrossRefGoogle Scholar
  58. 58.
    Zamzami N, Larochette N, Kroemer G. Mitochondrial permeability transition in apoptosis and necrosis. Cell Death Diff 2005; 12:1478–1480.CrossRefGoogle Scholar
  59. 59.
    Cande C, Cecconi F, Dessen P et al. Apoptosis-inducing factor (AIF): key to the conserved caspase-independent pathways of cell death? J Cell Sci 2002; 115:4727–4734.PubMedCrossRefGoogle Scholar
  60. 60.
    Lamkan M, Declercq W, Kalai M et al. Alice in caspase land. A phylogenetic analysis of caspases from worm to man. Cell Death Diff 2002; 9: 358–361.CrossRefGoogle Scholar
  61. 61.
    Green DR. Ten Minutes to Dead. Cell 2005; 121:671–674.PubMedCrossRefGoogle Scholar
  62. 62.
    Chakravarti D, Hong R. SET-ting the stage for life and death. Cell 2003; 112:589–593.PubMedCrossRefGoogle Scholar
  63. 63.
    Fan Z, Beresford PJ, Oh DY et al. Tumor suppressor NM23-H1 is a Granzyme A-activated DNase during CTL-mediated apoptosis, and the nucleosome assembly protein SET is its inhibitor. Cell 2003; 112:659–672.PubMedCrossRefGoogle Scholar
  64. 64.
    Almgren MAE, Henriksson KCE, Fujimoto J et al. Nucleoside diphosphate kinase A/nm23-H1 promotes metastasis of NB69-derived human neuroblastoma CE. Mol Cancer Res 2004; 2:387–394.PubMedGoogle Scholar
  65. 65.
    Chowdhury D, Beresford PJ, Zhu P et al. The exonuclease TREX1 is in the SET complex and acts in concert with NM23-H1 to degrade DNA during granzyme A-mediated cell death. Mol Cell 2006; 23:133–42.PubMedCrossRefGoogle Scholar
  66. 66.
    Goldtein P, Aubry L, Levraud J-P. Cell-death alternative model organisms: why and which? Nat Rev Mol Cell Biol 2003; 4:1–10.CrossRefGoogle Scholar
  67. 67.
    Koonin EV, Aravind L. Origin and evolution of eukaryotic apoptosis: the bacterial connection. Cell Death Diff 2002; 9:394–404.CrossRefGoogle Scholar
  68. 68.
    Yu YT, Snyder L. Translation elongation factor Tu cleaved by a phage exclusion system. Proc Natl Acad Sci USA 1994; 1:802–806.CrossRefGoogle Scholar
  69. 69.
    Lewis K. Programmed Death in Bacteria. Microb Mol Biol Rev 2000; 64:503–514.CrossRefGoogle Scholar
  70. 70.
    Berman-Frank I, Bidle K, Haramaty L et al. The demise of the marine cyanobacterium, Trichodesmium spp, via an autocatalyzed cell death pathway. Limnol Oceanogr 2004; 49:997–1005.Google Scholar
  71. 71.
    Ning SB, Guo HL, Wang L et al. Salt stress induces programmed cell death in prokaryotic organism Anabaena. J Appl Microbiol 2002; 93: 15–28.PubMedCrossRefGoogle Scholar
  72. 72.
    Bidle KB, Falkowski PG. Cell death planktonic photosynthetic microorganismes. Nat Rev Microb 2004; 2:643–655.CrossRefGoogle Scholar
  73. 73.
    Arnoult D, Tatischeff I, Estaquier J et al. On the evolutionary conservation of the cell death pathway: mitochondrial release of an apoptosis-inducing factor during Dictyostelium discoideum cell death. Mol Biol Cell 2001; 12:3016–3030.PubMedGoogle Scholar
  74. 74.
    Kosta A, Roisin-Bouffay C, Luciani MF et al. Autophagy gene disruption reveals a nonvacuolar cell death pathway in Dictyostelium. J Biol Chem 2004: 12:48404–48409.CrossRefGoogle Scholar
  75. 75.
    Kobayashi T, Endoh H. Caspase-like activity in programmed nuclear death during conjugation of Tetrahymena thermophila. Cell Death Diff 2003; 10:634–640.CrossRefGoogle Scholar
  76. 76.
    Kobayashi T, Endoh H. A possible role of mitochondria in the apoptotic-like programmed nuclear death of Tetrahymena thermophila. FEBS J 2005; 272:5378–87.PubMedCrossRefGoogle Scholar
  77. 77.
    Arnoult D, Akarid K, Grodet A et al. On the evolution of programmed cell death: apoptosis of the unicellular eukaryote Leishmania major involves cysteine proteinase activation and mitochondrion permeabilization. Cell Death Diff 2002; 9:65–81.CrossRefGoogle Scholar
  78. 78.
    Alzate J, Alvarez-Barrientos A, Gonzàlez VM et al. Heat-induced programmed cell death in Leishmania infantum is reverted by Bcl-XL expression. Apoptosis 2006; 11:161–171.PubMedCrossRefGoogle Scholar
  79. 79.
    Das M, Mukherjee SB, Shaha C. Hydrogen peroxide induces apoptosis-like death in Leishmania donovani promastigotes. J. Cell Sci 2001; 114:2461–2469.PubMedGoogle Scholar
  80. 80.
    Nguewa PA, Fuertes MA, Valladares B et al. Programmed cell death in trypanosomatids: a way to maximize their biological fitness? Trends Parasitol 2004; 20:375–379.PubMedCrossRefGoogle Scholar
  81. 81.
    Piacenza L, Peluffo G, Radi R. L-arginine-dependent suppression of apoptosis in Trypanosoma cruzi: contribution of the nitric oxide and polyamine pathways. Proc Natl Acad Sci USA 2001; 98:7301–7306.PubMedCrossRefGoogle Scholar
  82. 82.
    Welburn SC, Barcinski MA, Williams GT. Programmed cell death in trypanosomatids. Parasitol Today 1997; 13:22–6.PubMedCrossRefGoogle Scholar
  83. 83.
    Fedorova ND, Badger JH, Robson GD et al. Comparative analysis of programmed cell death pathways in filamentous fungi. BMC Genomics 2005; 6:177.PubMedCrossRefGoogle Scholar
  84. 84.
    Váchová L, Palková ZZ. Physiological regulation of yeast cell death in multicellular colonies is triggered by ammonia. J Cell Biol 2005; 5:711–717.CrossRefGoogle Scholar
  85. 85.
    Herker E, Jungwirth H, Katharina et al. Chronological aging leads to apoptosis in yeast. J Cell Biol 2004; 164:501–507.PubMedCrossRefGoogle Scholar
  86. 86.
    Al-Olayana EM, Williams GT, Hurd H. Apoptosis in the malaria protozoan, Plasmodium berghei: a possible mechanism for limiting intensity of infection in the mosquito. Int J Parasitol 2002; 32:1133–1143.CrossRefGoogle Scholar
  87. 87.
    Deponte M, Becker K. Plasmodium falciparum—do killers commit suicide? Trends Parasitol 2004; 20: 165–169.PubMedCrossRefGoogle Scholar
  88. 88.
    Brussaard CPD, Noordeloos AAM, Riegman R. Autolysis kinetics of the marine diatom Ditylum brightwellii (Bacillariophyceae) under nitrogen and phosphorus limitation and starvation. J Phycol 1997; 33:980–987.CrossRefGoogle Scholar
  89. 89.
    Berges JA, Charlebois DO, Mauzerall DC et al. Differential effects of nitrogen limitation on photosynthetic efficiency of photosystems I and II in microalgae. Plant Physiol 1996; 110:689–696.PubMedGoogle Scholar
  90. 90.
    Vardi A, Berman-Frank I, Rozenberg T et al. Programmed cell death of the dinoflagellate Peridinium gatunense is mediated by CO(2) limitation and oxidative stress. Curr Biol 1999; 9:1061–1064.PubMedCrossRefGoogle Scholar
  91. 91.
    Franklin DJ, Berges JA. Mortality in cultures of the dinoflagellate Amphidinium carterae during culture senescence and darkness. Proc Biol Sci 2004; 271:2099–2107.PubMedCrossRefGoogle Scholar
  92. 92.
    Berges JA, Charlebois DO, Mauzerall DC et al. Differential Effects of Nitrogen Limitation on Photosynthetic Efficiency of Photosystems I and II in Microalgae. Plant Physiol 1996; 110:689–696.PubMedGoogle Scholar
  93. 93.
    Segovia M, Haramaty L, Berges, JA. Cell death in the unicellular chlorophyte Dunaliella tertiolecta: a hypothesis on the evolution of apoptosis in higher plants and metazoans. Plant Physiol 2003; 132:99–105.PubMedCrossRefGoogle Scholar
  94. 94.
    Chose O, Noel C, Gerbod D et al. A form of cell death with some features resembling apoptosis in the amitochondrial unicellular organism Trichomonas vaginalis. Exp Cell Res 2002; 276:32–39.PubMedCrossRefGoogle Scholar
  95. 95.
    Chose O, Sarde CO, Noël C et al. Cell death in protists without mitochondria. Ann N Y Acad Sci 2003; 1010:121–125.PubMedCrossRefGoogle Scholar
  96. 96.
    Tan KS, Nasirudeen AM. Protozoan programmed cell death—insights from Blastocystis deathstyles Trends Parasitol 2005; 21:547–550.PubMedCrossRefGoogle Scholar
  97. 97.
    Rasoloson D, Vanacova S, Tomkova E. Mechanisms of in vitro development of resistance to metronidazole in Trichomonas vaginalis. Microbiology 2002; 148, 2467–2477.PubMedGoogle Scholar
  98. 98.
    Chose O, Sarde CO, Gerbod D et al. Programmed cell death in parasitic protozoans that lack mitochondria. Trends Parasitol 2003; 19:559–564.PubMedCrossRefGoogle Scholar
  99. 99.
    Nasirudeen AM, Tan KS, Singh M et al. Programmed cell death in a human intestinal parasite, Blastocystis hominis. Parasitology 2001; 123:235–246.PubMedCrossRefGoogle Scholar
  100. 100.
    Nasirudeen AM, Hian YE, Singh M et al. Metronidazole induces programmed cell death in the protozoan parasite Blastocystis hominis. Microbiology 2004; 150:33–43.PubMedCrossRefGoogle Scholar
  101. 101.
    Adam RD. Biology of Giardia lamblia Clin Microbiol 2001; 14:447–475.CrossRefGoogle Scholar
  102. 102.
    Benchimol M, Piva B, Campanati L. Visualization of the funis of Giardia lamblia by high-resolution field emission scanning electron microscopy—new insights. J Struct Biol 2004; 147:102–115.PubMedCrossRefGoogle Scholar

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© Landes Bioscience and Springer Science+Business Media 2008

Authors and Affiliations

  1. 1.Département de Génie BiologiqueUniversité de Technologie de CompiègneCompiègneFrance
  2. 2.Laboratoire Génie Enzymatique et Cellulaire, UMR CNRS 6022Université de Technologie de CompiègneCompiègne cedexFrance

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