Abstract
Programmed cell death is a genetically regulated process of cell suicide that is central to the development, homeostasis and integrity of multicellular organisms. Conversely, the dysregulation of mechanisms controlling cell suicide plays a role in the pathogenesis of a wide range of diseases. While great progress has been achieved in the unveiling of the molecular mechanisms of programmed cell death, a new level of complexity, with important therapeutic implications, has begun to emerge, suggesting (i) that several different self-destruction pathways may exist and operate in parallel in our cells, and (ii) that molecular effectors of cell suicide may also perform other functions unrelated to cell death induction and crucial to cell survival. In this review, I will argue that this new level of complexity, implying that there may be no such thing as a ‘bona fide’ genetic death program in our cells, might be better understood when considered in an evolutionary context. And a new view of the regulated cell suicide pathways emerges when one attempts to ask the question of when and how they may have become selected during evolution, at the level of ancestral single-celled organisms.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- APAF-1:
-
apoptotic protease-activating factor 1
- AIF:
-
apoptosis inducing factor
- TNFR:
-
tumor necrosis factor receptor
- DED:
-
death-effector domains
- CARD:
-
caspase activation and recruitment domains
- IAPs:
-
inhibitor of apoptosis proteins
References
Clarke PG, Clarke S . 1996 XIXth century research on naturally occurring cell death and related phenomena Anat. Embryol. (Berl) 193 : 81 – 99
Lockshin RA, Zakeri Z . 2001 Programmed cell death and apoptosis: origins of the theory Nat. Rev. Mol. Cell Biol 2 : 545 – 550
Glucksman A . 1951 Cell deaths in normal vertebrate ontogeny Biol. Rev. Camb. Philos. Soc 26 : 59 – 86
Lockshin RA, Williams CM . 1965 Programmed cell death: cytology of degeneration in the intersegmental muscles of the silkmoth J. Insect Physiol 11 : 123 – 133
Saunders JWJ . 1966 Death in the embryonic systems Science 154 : 604 – 612
Tata JR . 1966 Requirement for RNA and protein synthesis for induced regression of the tadpole tail in organ culture Dev. Biol 13 : 77 – 94
Kerr JFR, Willie AH, Currie AR . 1972 Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics Br. J. Cancer 26 : 239 – 257
Hamburger V, Brunso-Bechtold JK, Yip J . 1981 Neuronal death in the spinal ganglia of the chick embryo and its reduction by nerve growth factor J. Neurosci 1 : 60 – 71
Umansky S . 1982 The genetic program of cell death: hypothesis and some applications: transformation, carcinogenesis, ageing J. Theor. Biol 97 : 591 – 602
Cowan WM, Fawcett JW, O'Leary DDM, Stanfield BB . 1984 Regressive events in neurogenesis Science 225
Duke RC, Cohen JJ . 1986 IL-2 addiction: withdrawal of growth factor activates a suicide program in dependent T cells Lymphokine Res 5 : 289 – 299
Ellis HM, Horvitz HR . 1986 Genetic control of programmed cell death in the nematode C. elegans Cell 44 : 817 – 829
Levi-Montalcini R . 1987 Nerve growth factor: 35 years later Science 237 : 1154 – 1164
Vaux DL, Cory S, Adams JM . 1988 bcl-2 gene promotes haematopoietic cell survival and cooperates with c-myc to immortalize pre-B cells Nature 335 : 440 – 442
Clarke PG . 1990 Developmental cell death: morphological diversity and multiple mechanisms Anal. Embryol 181 : 195 – 213
Ellis RE, Yuan J, Horvitz HR . 1991 Mechanisms and functions of cell death Ann. Rev. Cell. Biol 7 : 663 – 698
Raff MC . 1992 Social controls on cell survival and cell death Nature 356 : 397 – 400
Vaux DL . 1993 Towards an understanding of the molecular mechanisms of physiological cell death Proc. Natl. Acad. Sci. USA 90 : 786 – 789
Hengartner M . 2000 The biochemistry of apoptosis Nature 407 : 770 – 776
Meier P, Finch A, Evan G . 2000 Apoptosis in development Nature 407 : 796 – 801
Rich T, Allen R, Wyllie A . 2000 Defying death after DNA damage Nature 407 : 777 – 783
Mehmet H . 2000 Caspases find a new place to hide Nature 403 : 29 – 30
Wang JM, Silva JP, Gustafsson CM, Rustin P, Larsson N-G . 2001 Increased in vivo apoptosis in cells lacking mitochondrial DNA gene expression Proc. Natl. Acad. Sci. USA 98 : 4038 – 4043
Jacobson MD, Weil M, Raff MC . 1997 Programmed cell death in animal development Cell 88 : 347 – 354
Vaux DL, Korsmeyer J . 1999 Cell death in development Cell 96 : 245 – 254
Oppenheim RW . 1991 Cell death during development of the nervous system Annu. Rev. Neurosci 14 : 453 – 501
Flanagan JG . 1999 Life on the road Nature 401 : 747 – 748
Goldrath A, Bevan M . 1999 Selecting and maintaining a diverse T-cell repertoire Nature 402 : 255 – 262
Yuan J, Yankner B . 2000 Apoptosis in the nervous system Nature 407 : 802 – 809
Clouston WM, Kerr JFR . 1985 Apoptosis, lymphocytotoxicity and the containment of viral infections Med. Hypothesis 18 : 399 – 404
Cohen JJ . 1993 Apoptosis Immunol. Today 14 : 126 – 130
Ameisen JC . 1994 Programmed cell death (apoptosis) and cell survival regulation: relevance to AIDS and cancer AIDS 8 : 1197 – 1213
Vaux DL, Haeker G, Strasser A . 1994 An evolutionary perspective on apoptosis Cell 76 : 777 – 779
Williams GT . 1994 PCD: a fundamental protective response to pathogens Trends Microbiol 12 : 463 – 464
Ameisen JC, Capron A . 1991 Cell dysfunction and depletion in AIDS: the programmed cell death hypothesis Immunol. Today 12 : 102 – 105
Clem RJ, Fechheimer M, Miller LK . 1991 Prevention of apoptosis by a baculovirus gene during infection of insect cells Science 254 : 1388 – 1390
Williams GT . 1991 Programmed cell death: apoptosis and oncogenesis Cell 65 : 1097 – 1098
Yonish-Rouach E, Resnitsky D, Lotem J, Sachs L, Kimchi A, Oren M . 1991 Wild-type p53 induces apoptosis of myeloid leukemic cells that is inhibited by IL-6 Nature 352 : 347 – 349
Ameisen JC, Estaquier J, Idziorek T . 1994 From AIDS to parasite infection: pathogen-mediated subversion of programmed cell death as a mechanism for immune dysregulation Immunol. Rev 142 : 9 – 51
Thompson CB . 1995 Apoptosis in the pathogenesis and treatment of disease Science 267 : 1456 – 1462
Nagata S, Golstein P . 1995 The Fas death factor Science 267 : 1449 – 1456
Teodoro JB, Branton PE . 1997 Regulation of apoptosis by viral gene products J. Virol 71 : 1739 – 1746
Zychlinski A, Sansonetti P . 1997 Apoptosis as a proinflammatory event: what we can learn from bacteria-induced cell death Trends Microbiol 5 : 201 – 204
Evan G, Littlewood T . 1998 A matter of life and death Science 281 : 1317 – 1322
Krammer P . 2000 CD95's deadly mission in the immune system Nature 407 : 789 – 795
Kerbel R . 1997 A cancer therapy resistant to resistance Nature 390 : 335 – 336
Gurney M, Tomasselli A, Heirikson R . 2000 Stay the executioner's hand Science 288 : 283 – 284
Nicholson DW . 2000 From bench to clinic with apoptosis based therapeutic agents Nature 407 : 810 – 816
Migliaccio E, Giorgio M, Mele S, Pelicci G, Reboldi P, Pandolfi PP, Lanfrancone L, Pelicci PG . 1999 The p66shc adaptor protein controls oxidative stress response and life-span in mammals Nature 402 : 309 – 313
Kerr JF . 1965 A histochemical study of hypertrophy and ischaemic injury of rat liver with special reference to changes in lysosomes J. Pathol. Bacteriol 90 : 419 – 435
Kerr JF . 1971 Shrinkage necrosis: a distinct mode of cellular death J. Pathol 105 : 13 – 20
Lockshin RA . 1997 The early modern period of cell death Cell Death Differ 4 : 347 – 351
Ameisen JC . 1999 La Sculpture du vivant. Le suicide cellulaire ou la mort créatrice 2nd edn 2000 Paris: Editions du Seuil Al Cuore della vita 2nd edn 2001 Milano: Feltrinelli
Melino G . 2001 Concept: The Sirens' song Nature 412 : 23
Lewontin R . 2000 The Triple helix. Gene organism and environment Cambridge, Ma.: Harvard University Press
Savill J, Fadok V . 2000 Corpse clearance defines the meaning of cell death Nature 407 : 784 – 788
Green DR, Beere HM . 2000 Apoptosis: Gone but not forgotten Nature 405 : 28 – 29
Schwartz LM, Smith S, Jones MEE, Osborne BA . 1993 Do all programmed cell deaths occur via apoptosis? Proc. Natl. Acad. Sci. USA 90 : 980 – 984
Sperandio S, deBelle I, Bredesen D . 2000 An alternative non apoptotic form of programmed cell death Proc. Natl. Acad. Sci. USA 97 : 14376 – 14381
Wyllie AH, Golstein P . 2001 More than one way to go Proc. Natl. Acad. Sci. USA 98 : 11 – 13
Samali A, Zhivotovsky B, Jones D, Nagata S, Orrenius S . 1999 Apoptosis: cell death defined by caspase activation Cell Death Differ 6 : 495 – 496
Vaux DL . 1999 Caspases and apoptosis – biology and terminology Cell Death Differ 6 : 493 – 494
Steller H . 1995 Mechanisms and genes of cellular suicide Science 267 : 1445 – 1449
Cikala M, Wilm B, Hobmayer E, Bottger A, David CN . 1999 Identification of caspases and apoptosis in the simple metazoan Hydra Curr Biol 9 : 959 – 962
Sulston JE . 1976 Post-embryonic development in the ventral cord of Caenorhabditis elegans Philos. Trans. R. Soc. Lond. B. Biol. Sci 275 : 287 – 297
Sulston JE, Horvitz HR . 1977 Post-embryonic cell lineages of the nematode, Caenorhabditis elegans Dev. Biol 56 : 110 – 156
Hedgecock EM, Sulston JE, Thomson JN . 1983 Mutations affecting programmed cell deaths in the nematode Caenorhabditis elegans Science 220 : 1277 – 1279
Horvitz HR, Sternberg PW, Greenwald IS, Fixsen W, Ellis HM . 1983 Mutations that affect neural cell lineages and cell fates during the development of the nematode Caenorhabditis elegans Cold Spring Harb. Symp. Quant. Biol 48 : Pt 2 453 – 463
Horvitz HR . 1999 Genetic control of programmed cell death in the nematode Caenorhabditis elegans Canc. Res 59 Suppl : 1701 – 1706
Hoeppner DJ, Hengartner MO, Schnabel R . 2001 Engulfment genes cooperate with ced-3 to promote cell death in Caenorhabditis elegans Nature 412 : 202 – 206
Reddien PW, Cameron S, Horvitz HR . 2001 Phagocytosis promotes programmed cell death in C. elegans Nature 412 : 198 – 202
Wiens M, Diehl-Seifert B, Muller WE . 2001 Sponge Bcl-2 homologous protein (BHP2-GC) confers distinct stress resistance to human HEK-293 cells Cell Death Differ 8 : 887 – 898
Inohara N, Nunez G . 2000 Genes with homology to mammalian apoptosis regulators identified in zebrafish Cell Death Differ 7 : 509 – 510
Yuan J, Shaham S, Ledoux S, Ellis HM, Horvitz HR . 1993 The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1β converting enzyme Cell 75 : 641 – 652
Hengartner MO, Horvitz HR . 1994 C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2 Cell 76 : 665 – 676
Vaux DL, Weissman IL, Kim SK . 1992 Prevention of programmed cell death in c. elegans by human bcl-2 Science 258 : 1955 – 1957
Finkel E . 2001 The mitochondrion: is it central to apoptosis? Science 292 : 624 – 626
Gross A, McDonnell JM, Korsmeyer SJ . 1999 Bcl-2 family members and the mitochondria in apoptosis Genes Dev 13 : 1899 – 1911
Vander Herden M, Thompson C . 1999 Bcl-2 proteins: regulators of apoptosis or of mitochondrial homeostasis? Nature Cell. Biol 1 : 209 – 216
Green DR . 2000 Apoptotic pathways: Paper wraps stone blunt scissors Cell 102 : 1 – 4
Kroemer G, Reed J . 2000 Mitochondrial control of cell death Nature Med 6 : 513 – 519
Martinou JC, Green D . 2001 Breaking the mitochondrial barrier Nat. Rev. Mol. Cell. Biol 2 : 63 – 67
Suzuki Y, Imai Y, Nakayama H, Takahashi K, Takio K, Takahashi R . 2001 A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death Mol. Cell 8 : 613 – 621
Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, Mangion J, Jacotot E, Costantini P, Loeffler M, Larochette N, Goodlett DR, Aebersold R, Siderovski DP, Penninger JM, Kroemer G . 1999 Molecular characterization of mitochondrial apoptosis-inducing factor Nature 397 : 441 – 446
Li LY, Luo X, Wang X . 2001 Endonuclease G is an apoptotic DNase when released from mitochondria Nature 412 : 95 – 99
Nagata S . 2000 Apoptotic DNA fragmentation Exp. Cell. Res 256 : 12 – 18
Thornberry NA, Lazebnik Y . 1998 Caspases: enemies within Science 281 : 1312 – 1316
Goyal L . 2001 Cell death inhibition: keeping caspases in check Cell 104 : 805 – 808
Li K, Li Y, Shelton JM, Richardson JA, Spencer E, Chen ZJ, Wang X, Williams RS . 2000 Cytochrome c deficiency causes embryonic lethality and attenuates stress-induced apoptosis Cell 101 : 389 – 399
Joza N, Susin SA, Daugas E, Stanford WL, Cho SK, Li CY, Sasaki T, Elia AJ, Cheng HY, Ravagnan L, Ferri KF, Zamzami N, Wakeham A, Hakem R, Yoshida H, Kong YY, Mak TW, Zuniga-Pflucker JC, Kroemer G, Penninger JM . 2001 Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death Nature 410 : 549 – 554
Reed J . 1999 Splicing and dicing apoptosis genes Nature Biotechnol 17 : 1064 – 1065
Aravind L, Dixit VM, Koonin EV . 2001 Apoptotic molecular machinery: vastly increased complexity in vertebrates revealed by genome comparisons Science 291 : 1279 – 1284
Speliotes EK, Uren A, Vaux D, Horvitz HR . 2000 The survivin-like C. elegans BIR-1 protein acts with the Aurora-like kinase AIR-2 to affect chromosomes and the spindle midzone Mol. Cell 6 : 211 – 223
Xiang J, Chao DT, Korsmeyer SJ . 1996 Bax-induced cell death may not require ICE-like proteases Proc. Natl. Acad. Sci. USA 93 : 14559 – 14563
McCarthy NJ, Whyte MK, Gilbert CS, Evan GI . 1997 Inhibition of Ced-3/ICE-related proteases does not prevent cell death induced by oncogenes, DNA damage, or the Bcl-2 homologue Bak J. Cell. Biol 136 : 215 – 227
Deas O, Dumont C, MacFarlane M, Rouleau M, Hebib C, Harper F, Hirsch F, Charpentier B, Cohen GM, Senik A . 1998 Caspase-independent cell death induced by anti-CD2 or staurosporine in activated human peripheral T lymphocytes J. Immunol 161 : 3375 – 3383
Quignon F, De Bels F, Koken M, Feuteun J, Ameisen JC, de Thé H . 1998 PML induces a novel caspase-independent death process Nature Genetics 20 : 259 – 265
Vercammen D, Brouckaert G, Denecker G, Van de Craen M, Declercq W, Fiers W, Vandenabeele P . 1998 Dual signaling of the Fas receptor: initiation of both apoptotic and necrotic cell death pathways J. Exp. Med 188 : 919 – 930
Chautan M, Chazal G, Cecconi F, Gruss P, Golstein P . 1999 Interdigital cell death can occur through a necrotic and caspase-independent pathway Curr. Biol 9 : 967 – 970
Holler N, Zaru R, Micheau O, Thome M, Attinger A, Valitutti S, Bodmer JL, Schneider P, Seed B, Tschopp J . 2000 Fas triggers an alternative caspase 8-independent cell death pathway using kinase RIP as effector molecule Nature Immunology 1 : 489 – 495
Parrish J, Li L, Klotz K, Ledwich D, Wang X, Xue D . 2001 Mitochondrial endonuclease G is important for apoptosis in C. elegans Nature 412 : 90 – 94
Evan GA . 1994 Old cells never die, they just apoptose Trends Cell. Biol 4 : 191 – 192
Greenberg JT . 1996 Programmed cell death: a way of life for plants Proc. Natl. Acad. Sci. USA 93 : 12094 – 12097
Beers EP . 1997 Programmed cell death during plant growth and development Cell Death Differ 4 : 649 – 661
Rubinstein B, Osborne B . 1997 Dying for a living: plants do it Cell Death Differ 4 : 647 – 648
Mittler R . 1998 Cell death in plants In When Cells Die Lockshin R, Zakeri Z and Tilly J, eds New York: Wiley-Liss, Inc pp 147 – 174
Greenberg J, Guo A, Klessig D, Ausubel F . 1994 Programmed cell death in plants: a pathogen-triggered response activated coordinately with multiple defence functions Cell 77 : 551
Levine A, Pennel RI, Alvarez ME, Palmer R, Lamb C . 1996 Calcium-mediated apoptosis in plant hypersensitive disease resistance response Curr. Biol 6 : 427 – 437
Solomon M, Belenghi B, Delledonne M, Menachem E, Levine A . 1999 The involvement of cysteine proteases and protease inhibitor genes in the regulation of programmed cell death in plants Plant Cell 11 : 431 – 444
DelPoso O, Lam E . 1998 Caspases and programmed cell death in the hypersensitive response of plants to pathogens Curr. Biol 8 : 1129 – 1132
Uren A, O'Rourke K, Aravind L, Pisabarro M, Seshagiri S, Koonin E, Dixit V . 2000 Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma Mol. Cell 6 : 961 – 967
Balk J, Leaver CJ, McCabe PF . 1999 Translocation of cytochrome c from the mitochondria to the cytosol occurs during heat-induced programmed cell death in cucumber plants FEBS Lett 463 : 151 – 154
Mitsuhara I, Malik KA, Miura M, Ohashi Y . 1999 Animal cell-death suppressors Bcl-xL and Ced-9 inhibit cell death in tobacco plants Curr. Biol 9 : 775 – 778
Lacomme C, Santa Cruz S . 1999 Bax-induced cell death in tobacco is similar to the hypersensitive response Proc. Natl. Acad. Sci. USA 96 : 7956 – 7961
Clem R, Duckett C . 1997 The iap genes: unique arbitrators of cell death Trends Cell Biol 7 : 337 – 339
Ameisen JC . 1998 HIV: Setting death in motion Nature 395 : 117 – 119
Ameisen JC . 2001 Apoptosis subversion: HIV-Nef provides both armor and sword Nat. Med 7 : 1181 – 1182
Freire-de-Lima CG, Nascimento DO, Soares MBP, Bozza PT, Castro-Faria-Neto HC, de Mello FG, DosReis GA, Lopes MF . 2000 Uptake of apoptotic cells drives the growth of a pathogenic trypanosome in macrophages Nature 403 : 199 – 203
vanValen L . 1973 A new evolutionary law Evol. Theory I : 1 – 30
Sogin ML . 1991 Early evolution and the origin of eukaryotes Curr. Op. Gen. Dev 1 : 457 – 463
Doolittle RF, Feng DF, Tsang S, Cho G, Little E . 1996 Determining divergence times of the major kingdoms of living organisms with a protein clock Science 271 : 470 – 477
Ucker DS . 1991 Death by suicide: one way to go in mammalian cellular development? The New Biologist 3 : 103 – 109
Dawkins R . 1982 The Extended phenotype Oxford University Press
Dawkins R . 1986 The Blind watchmaker Longman
Sigmund K . 1993 Games of Life Oxford University Press
Oliver G, Gruss P . 1997 Current views on eye development Trends Neurol. Sci 9 : 415 – 421
Janeway CA Jr, Travers P . 2000 Immunobiology. The immune system in health and disease Curr. Biol
Agrawal A, Eastman Q, Schatz D . 1998 Transposition-mediated by RAG1 and RAG2 and its implications for the evolution of the immune system Nature 394 : 744 – 751
Plasterk R . 1998 V(D)J recombination: ragtime jumping Nature 394 : 718 – 719
Ameisen JC, Idziorek T, Billaut-Mulot O, Loyens M, Tissier JP, Potentier A, Ouaissi MA . 1995 Apoptosis in a unicellular eukaryote (Trypanosoma cruzi): implications for the evolutionary origin and role of programmed cell death in the control of cell proliferation, differentiation and survival Cell Death Differ 2 : 285 – 300
Ameisen JC . 1996 The origin of programmed cell death Science 272 : 1278 – 1279
Ameisen JC . 1998 The evolutionary origin and role of programmed cell death in single celled organisms: a new view of executioners, mitochondria, host-pathogen interactions, and the role of death in the process of natural selection In When cells die Lockshin R, Zakeri Z and Tilly J, eds New York: Wiley-Liss, Inc pp 3 – 56
Piacenza L, Peluffo G, Radi R . 2001 L-arginine-dependent suppression of apoptosis in Trypanosoma cruzi: contribution of the nitric oxide and polyamine pathways Proc. Natl. Acad. Sci. USA 98 : 7301 – 7306
Welburn SC, Dale C, Ellis D, Beecroft R, Pearson TW . 1996 Apoptosis in procyclic Trypanosoma brucei rhodesiense in vitro Cell Death Differ 3 : 229 – 236
Ridgley EL, Xiong ZH, Ruben L . 1999 Reactive oxygen species activate a Ca++-dependent cell death pathway in the unicellular organism Trypanosoma brucei brucei Biochem. J 340 : Pt 1 33 – 40
Moreira MEC, DelPortillo HA, Milder RV, Balanco JM, Barcinski MA . 1996 Heat shock induction of apoptosis in promastigotes of the unicellular organism Leishmania amazonensis J. Cell. Physiol 167 : 305 – 313
Das M, Mukherjee SB, Shaha C . 2001 Hydrogen peroxide induces apoptosis-like death in Leishmania donovani promastigotes J. Cell. Sci 114 : 2461 – 2469
Lee N, Bertholet S, Debrabant A, Muller J, Duncan R, Nakhasi HL . 2002 Programmed cell death in the unicellular protozoan parasite Leishmania Cell Death Differ 9 : 53 – 64
Arnoult D, Akarid K, Grodet A, Petit PX, Estaquier J, Ameisen JC . 2002 On the evolution of programmed cell death: apoptosis of the unicellular eukaryote Leishmania major involves cysteine proteinase activation and mitochondrion permeabilization Cell Death Differ 9 : 65 – 81
Cornillon S, Foa C, Davoust J, Buonavista N, Gross JD, Golstein P . 1994 Programmed cell death in Dictyostelium J. Cell. Sci 107 : 2691 – 2704
Kaiser D . 1986 Control of multicellular development: Dictyostelium and Myxococcus Annu. Rev. Genet 20 : 536 – 566
Christensen ST, Wheatley DN, Rasmussen MI, Rasmussen L . 1995 Mechanisms controlling death, survival and proliferation in a model unicellular eukaryote Tetrahymena thermophila Cell Death Differ 2 : 301 – 308
Vardi A, Berman-Frank I, Rozenberg T, Hadas O, Kaplan A, Levine A . 1999 Programmed cell death of the dinoflagellate Peridinium gatunense is mediated by CO2 limitation and oxidative stress Curr. Biol 9 : 1061 – 1064
Madeo F, Fröhlich E, Ligr M, Grey M, Sigrist SJ, Wolf DH, Fröhlich KU . 1999 Oxygen stress: a regulator of apoptosis in yeast J. Cell. Biol 145 : 757 – 767
Fraser A, James C . 1998 Fermenting debate: do yeast undergo apoptosis? Trends Cell. Biol 8 : 219 – 221
Matsuyama S, Reed J . 1999 Yeasts as tool for apoptosis research Curr. Op. Microbiol 2 : 618 – 623
Maslov DA, Simpson L . 1995 Evolution of parasitism in kinetoplastid protozoa Parasitol. Today 11 : 30 – 32
Wittingham WF, Raper KB . 1960 Non-viability of stalk cells in Dictyostelium discoideum Proc. Natl. Acad. Sci. USA 46 : 642 – 649
Wildermuth H . 1970 Development and organization of the aerial mycelium in Streptomyces coelicolor J. Gen. Microbiol 60 : 43 – 50
Wireman J, Dworkin M . 1975 Morphogenesis and developmental interaction in Myxobacteria Science 189 : 516 – 523
Kalakoutskii LV, Agre NS . 1976 Comparative aspects of development and differentiation in actinomycetes Bacteriol. Rev 40 : 469 – 524
Wireman J, Dworkin M . 1977 Developmentally-induced autolysis during fruiting body formation by Myxococcus xanthus J. Bacteriol 129 : 796 – 802
Kühn TS . 1970 The structure of scientific revolutions 2nd edn Chicago: University of Chicago Press
Lightman A, Gingerich O . 1991 When do anomalies begin? Science 255 : 690 – 695
Kaiser D, Losick R . 1993 How and why bacteria talk to each other Cell 73 : 873 – 885
Davis MC, Ward JG, Herrick G, Allis CD . 1992 Programmed nuclear death: apoptotic-like degradation of specific nuclei in conjugating Tetrahymena Dev. Biol 154 : 419 – 432
Counis MF, Chaudun E, Arruti C, Oliver L, Sanwal M, Courtois Y, Torriglia A . 1998 Analysis of nuclear degradation during lens cell differentiation Cell Death Differ 5 : 251 – 261
Olie RA, Durrieu F, Cornillon S, Loughran G, Gross J, Earnshow WC, Golstein P . 1998 Apparent caspase independence of programmed cell death in Dictyostelium Curr. Biol 8 : 955 – 958
Tatischeff I, Petit PX, Grodet A, Tissier JP, Duband-Goulet I, Ameisen JC . 2001 Inhibition of multicellular development switches cell death of Dictyostelium discoideum towards mammalian-like unicellular apoptosis Eur. J. Cell. Biol 80 : 428 – 441
Arnoult D, Tatischeff I, Estaquier J, Girard M, Sureau F, Tissier JP, Grodet A, Dellinger M, Traincard F, Kahn A, Ameisen JC, Petit PX . 2001 On the evolutionary conservation of the cell death pathway: mitochondrial release of an Apoptosis-Inducing Factor during Dictyostelium discoideum cell death Mol. Biol. Cell 12 : 3016 – 3300
Hanada M, Aimé-Sempé C, Sato T, Reed JC . 1995 Structure-function analysis of Bcl-2 protein. Identification of conserved domains important for homodimerization with Bcl-2 and heterodimerization with Bax J. Biol. Chem 270 : 11962 – 11969
Shimizu S, Shinohara Y, Tsujimoto Y . 2000 Bax and Bcl-xL independently regulate apoptotic changes of yeast mitochondria that require VDAC but not adenine nucleotide translocator Oncogene 19 : 4309 – 4318
Roucou X, Prescott M, Devenish RJ, Nagley P . 2000 A cytochrome c-GFP fusion is not released from mitochondria into the cytoplasm upon expression of Bax in yeast cells FEBS Lett 471 : 235 – 239
Gross A, Pilcher K, Blachly-Dyson E, Basso E, Jockel J, Bassik MC, Korsmeyer SJ, Forte M . 2000 Biochemical and genetic analysis of the mitochondrial response of yeast to Bax and Bcl-xL Mol. Cell. Biol 20 : 3125 – 3136
James C, Geschmeissner S, Fraser A, Evan G . 1997 Ced-4 induces chromatin condensation in S. pombe and is inhibited by direct physical association with Ced-9 Curr. Biol 7 : 246 – 252
Goldmacher VS, Bartle LM, Skaletskaya A, Dionne CA, Kedersha NL, Vater CA, Han JW, Lutz RJ, Watanabe S, Cahir McFarland ED, Kieff ED, Mocarski ES, Chittenden T . 1999 A cytomegalovirus-encoded mitochondria-localized inhibitor of apoptosis structurally unrelated to Bcl-2 Proc. Natl. Acad. Sci. USA 96 : 12536 – 12541
Lorenzo H, Susin S, Penninger J, Kroemer G . 1999 Apoptosis inducing factor (AIF): a phylogenetically old, caspase-independent effector of cell death Cell Death Differ 6 : 516 – 524
Hengartner M . 2001 Apoptosis: DNA destroyers Nature 412 : 27 – 29
Dacks JB, Doolittle WF . 2001 Reconstructing/Deconstructing the earliest eukaryotes. How comparative genomics can help Cell 107 : 419 – 425
Jensen RB, Gerdes K . 1995 Programmed cell death in bacteria: proteic plasmid stabilization systems Mol. Microbiol 17 : 205 – 210
Yarmolinsky MB . 1995 Programmed cell death in bacterial populations Science 267 : 836 – 837
Franch T, Gerdes K . 1996 Programmed cell death in bacteria: translational repression by mRNA end-pairing Mol. Microbiol 21 : 1049 – 1060
Miguelez EM, Hardisson C, Manzanal MB . 1999 Hyphal death during colony development in Streptomyces antibioticus: morphological evidence for the existence of a process of cell deletion in a multicellular prokaryote J. Cell. Biol 145 : 515 – 525
Liu J . 1994 Microcin B17: post-translational modifications and their biological implications Proc. Natl. Acad. Sci. USA 91 : 4618 – 4620
Nordström K, Austin SJ . 1989 Mechanisms that contribute to the stable segregation of plasmids Annu. Rev. Genet 23 : 37 – 69
Gerdes K, Rasmunssen PB, Molin S . 1986 Unique type of plasmid maintenance function: postsegregational killing of plasmid-free cells Proc. Natl. Acad. Sci. USA 83 : 3116 – 3120
Katayama Y, Gottesman S, Pumphrey J, Rudikkoff S, Clark WP, Maurizi MR . 1988 The two-component, ATP-dependent Clp protease of Escherichia coli J. Biol. Chem 263 : 15226 – 15236
Snyder L . 1995 Phage-exclusion enzymes: a bonanza of biochemical and cell biology reagents? Mol. Microbiol 15 : 415 – 420
Dawkins R . 1976 The Selfish gene Oxford University Press
Bull JJ, Molineux IJ, Werren JH . 1992 Selfish genes Science 256 : 65
Hurst LD, Pomiankowski A . 1998 Sexual selection: the eyes have it Nature 391 : 223 – 224
Naito T, Kusano K, Kobayashi I . 1995 Selfish behavior of restriction-modification systems Science 267 : 897 – 899
Aizenman E, Engelberg-Kulka H, Glaser G . 1996 An Escherichia coli chromosomal ‘addiction module’ regulated by 3′,5′-bispyrophospate: a model for programmed bacterial cell death Proc. Natl. Acad. Sci. USA 93 : 6059 – 6063
Losick R, Stragier P . 1992 Crisscross regulation of cell-type-specific gene expression during development in B. subtilis Nature 355 : 601 – 604
Hengge-Aronis R . 1993 Survival of hunger and stress: the role of rpoS in early stationary phase gene regulation in E. coli Cell 72 : 165 – 168
Kaiser D . 1996 Bacteria also vote Science 272 : 1598 – 1599
Ohta N, Newton A . 1996 Signal transduction in the cell cycle regulation of Caulobacter differentiation Trends Microbiol 4 : 326 – 332
Costerton JW, Stewart PS, Greenberg EP . 1999 Bacterial biofilms: a common cause of persistent infections Science 284 : 1318 – 1322
Velicer GJ, Kroos L, Lenski RE . 2000 Developmental cheating in the social bacterium Myxococcus xanthus Nature 404 : 598 – 601
Novak J . 1996 Programmed cell death (Response) Science 274 : 20
Ameisen JC . 1996 Programmed cell death (Response) Science 274 : 20 – 21
Shapiro L . 1993 Protein localization and asymmetry in the bacterial cell Cell 73 : 841
Errington J . 1996 Determination of cell fate in Bacillus subtilis Trends Genet 12 : 31 – 34
Arigoni F, Pogliano K, Webb CD, Stragier P, Losick R . 1995 Localization of protein implicated in establishment of cell type to sites of asymmetric division Science 270 : 637 – 640
Nugroho FA, Yamamoto H, Kobayashi Y, Sekiguchi J . 1999 Characterization of a new sigma-K-dependent peptidoglycan hydrolase gene that plays a role in Bacillus subtilis mother cell lysis J. Bacteriol 181 : 6230 – 6237
Kauffman SA . 1993 The origins of order. Self-organization and selection in evolution Oxford University Press
Kirschner M, Gerhart J, Mitchison T . 2000 Molecular ‘vitalism’ Cell 100 : 79 – 88
Jan Y, Jan L . 1998 Asymmetric cell division Nature 392 : 775 – 778
Amon A . 1996 Mother and daughter are doing fine: asymmetric cell division in yeast Cell 84 : 651 – 654
Söderbom F, Loomis WF . 1998 Cell-cell signaling during Dictyostelium development Trends Microbiol 6 : 402 – 406
Margulis L . 1981 Symbiosis in Cell Evolution New York: W.H. Freeman
Margulis L, Sagan D . 1997 Microcosmos. Four billion years of microbial evolution University of California Press First published by Summit Books1986
Martin W, Müller M . 1998 The hydrogen hypothesis for the first eukaryote Nature 392 : 37 – 41
Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD . 1994 Molecular Biology of the Cell New York: Garland Publishing, Inc
Lewin B . 1997 Genes VI (Oxford, New York, Tokyo): Oxford University Press, Inc
Doolittle W . 1998 Eukaryote origins: a paradigm gets shifty Nature 392 : 15 – 16
Ménard R, Dehio C, Sansonetti PJ . 1996 Bacterial entry into epithelial cells: the paradigm of Schigella Trends Microbiol 4 : 220 – 226
Rousset F, Bouchon D, Pintureau B, Juchault P, Solignac M . 1992 Nucleotide Wolbachia endosymbionts responsible for various alterations of sexuality in arthropods Proc. R. Soc. Lond. B. Biol. Sci 250 1328 : 91 – 98
Rigaud T, Rigaud PJ . 1993 Conflict between feminizing sex ratio distorters and an autosomal masculinizing gene in the terrestrial isopod Armadillidium vulgare Latr Genetics 133 : 247 – 252
Jeon KW, Jeon MS . 1976 Endosymbiosis in amoebae: recently established endosymbionts have become required cytoplasmic components J. Cell. Physiol 89 : 337 – 344
Palmer JD . 1997 Organelle genomes: going, going, gone! Science 275 : 790 – 791
Zamzami N, Kroemer G . 2001 The mitochondrion in apoptosis: how Pandora's box opens Nat. Rev. Mol. Cell. Biol 2 : 67 – 71
Jacobson MD, Burne JF, King MP, Miyashita T, Reed JC, Raff MC . 1993 Bcl-2 blocks apoptosis in cells lacking mitochondrial DNA Nature 361 : 365 – 369
Muchmore SW, Sattlet M, Liang H, Meadows RP, Harlan JE, Yoon HS, Nettesheim D, Chang BS, Thompson CB, Wong SL, Ng SL, Fesik SW . 1996 X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death Nature 381 : 335 – 341
Harrington EA, Fanidi A, Evan GI . 1994 Oncogenes and cell death Curr. Op. Gen. Dev 4 : 120 – 129
Shi L, Nishioka WK, Th'ng J, Bradbury EM, Litchfield DW, Greenberg AH . 1994 Premature p34cdc2 activation required for apoptosis Science 263 : 1143 – 1145
Lundgren K, Walmorth N, Booker R, Dembski M, Kirschner M, Beach D . 1991 mik1 and wee1 cooperate in the inhibitory tyrosine phosphorylation of cdc2 Cell 64 : 1111 – 1122
Heald R, McLoughlin M, McKeon F . 1993 Human wee1 maintains mitotic timing by protecting the nucleus from cytoplasmically activated cdc2 kinase Cell 74 : 463 – 474
Oshida T, Sugai M, Komatsuzawa H, Hong YM, Suginaka H, Tomasz A . 1995 A Staphylococcus aureus autolysin that has an N-acetylmuramoyl-L-alanine amidase domain and an endo-β-N-acetylglucosaminidase domain: cloning, sequence analysis, and characterization Proc. Natl. Acad. Sci. USA 92 : 285 – 289
Knoll AH . 1992 The early evolution of eukaryotes: a geological perspective Science 256 : 622 – 627
Forterre P . 1996 A hot topic: the origin of hyperthermophiles Cell 85 : 789 – 792
Golstein P . 1998 Cell death in us and others Science 281 : 1283
Xue L, Fletcher G, Tolkovsky A . 2001 Mitochondria are selectively eliminated from eukaryotic cells after blockade of caspases during apoptosis Curr. Biol 11 : 361 – 365
Kitanaka C, Kuchino Y . 1999 Caspase-independent programmed cell death with necrotic morphology Cell Death Differ 6 : 508 – 515
Lee CY, Baehrecke EH . 2001 Steroid regulation of autophagic programmed cell death during development Development 128 : 1443 – 1455
Foghsgaard L, Wissing D, Mauch D, Lademann U, Bastholm L, Boes M, Elling F, Leist M, Jaattela M . 2001 Cathepsin B acts as a dominant execution protease in tumor cell apoptosis by TNF J. Cell. Biol 153 : 999 – 1009
Bratosin D, Estaquier J, Petit F, Arnoult D, Quatannens B, Tissier JP, Slomianny C, Sartiaux C, Alonso C, Huart JJ, Montreuil J, Ameisen JC . 2001 Programmed cell death in mature erythrocytes: a model for investigating death effector pathways operating in the absence of mitochondria Cell Death Differ 8 : 1143 – 1156
Berg CP, Engels IH, Rothbart A, Lauber K, Renz A, Schlosser SF, Schulze-Osthoff K, Wesselborg S . 2001 Human mature red blood cells express caspase-3 and caspase-8, but are devoid of mitochondrial regulators of apoptosis Cell Death Differ 8 : 1197 – 1206
Dumont C, Dürrbach A, Bidère N, Rouleau M, Kroemer G, Bernard G, Hirsch F, Charpentier B, Susin SA, Senik A . 2000 Caspase-independent commitment phase to apoptosis in activated blood T lymphocytes: reversibility at low apoptotic insult Blood 96 : 1030 – 1038
Zeuner A, Eramo A, Peschle C, De Maria R . 1999 Caspase activation without death Cell Death Differ 6 : 1075 – 1080
Alam A, Cohen LY, Aouad S, Sékaly RP . 1999 Early activation of caspases during T lymphocyte stimulation results in selective substrate cleavage in nonapoptotic cells J. Exp. Med 190 : 1879 – 1890
DeMaria R, Zeuner A, Eramo A, Domenichelli C, Bonci D, Grignani F, Srinivasula SM, Alnemri ES, Testa U, Peschle C . 1999 Negative regulation of erythropoiesis by caspase-mediated cleavage of GATA-1 Nature 401 : 489 – 493
Elkon K . 1999 Caspases: multifunctional proteases J. Exp. Med 190 : 1725 – 1727
Kennedy NJ, Kataoka T, Tschopp J, Budd RC . 1999 Caspase activation is required for T cell proliferation J. Exp. Med 190 : 1891 – 1896
Los M, Stroh C, Janicke RU, Engels IH, Schulze-Osthoff K . 2001 Caspases: more than just killers? Trends Immunol 22 : 31 – 34
Zermati Y, Garrido C, Amsellem S, Fishelson S, Bouscary D, Valensi F, Varet B, Solary E, Hermine O . 2001 Caspase activation is required for terminal erythroid differentiation J. Exp. Med 193 : 247 – 254
Cote J, Ruiz-Carrillo A . 1993 Primers for mitochondrial DNA replication generated by endonuclease G Science 261 : 765 – 769
Frank S, Gaume B, Bergmann-Leitner ES, Leitner WW, Robert EG, Catez F, Smith CL, Youle RJ . 2001 The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis Dev. Cell 1 : 515 – 525
Driscoll M, Chalfie M . 1991 The mec-4 gene is a member of a family of Caenorhabditis elegans genes that can mutate to induce neuronal degeneration Nature 349 : 588 – 593
Hall DH, Gu G, Garcia-Anoveros J, Gong L, Chalfie M, Driscoll M . 1997 Neuropathology of degenerative cell death in Caenorhabditis elegans J. Neurosci 17 : 1033 – 1045
Korswagen HC, vanderLinden AM, Plasterk RH . 1998 G protein hyperactivation of the Caenorhabditis elegans adenylyl cyclase SGS-1 induces neuronal degeneration EMBO J 17 : 5059 – 5065
Xu K, Tavernarakis N, Driscoll M . 2001 Necrotic cell death in C. elegans requires the function of calreticulin and regulators of Ca++ release from the endoplasmic reticulum Neuron 31 : 957 – 971
Derry WB, Putzke AP, Rothman JH . 2001 Caenorhabditis elegans p53: role in apoptosis, meiosis, and stress resistance Science 294 : 591 – 595
Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer D . 1997 The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis Science 275 : 1132 – 1136
Rep M, vanDijl JM, Suda K, Schatz G, Grivell LA, Suzuki CK . 1996 Promotion of mitochondrial membrane complex assembly by a proteolytically inactive yeast Lon Science 274 : 103 – 106
Author information
Authors and Affiliations
Corresponding author
Additional information
Edited by G Melino
Rights and permissions
About this article
Cite this article
Ameisen, J. On the origin, evolution, and nature of programmed cell death: a timeline of four billion years. Cell Death Differ 9, 367–393 (2002). https://doi.org/10.1038/sj.cdd.4400950
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/sj.cdd.4400950
Keywords
This article is cited by
-
Cell death of Acanthamoeba castellanii following exposure to antimicrobial agents commonly included in contact lens disinfecting solutions
Parasitology Research (2024)
-
Pyrazole-sulfonamide scaffold featuring dual-tail strategy as apoptosis inducers in colon cancer
Scientific Reports (2023)
-
Ursolic Acid Promotes Autophagy by Inhibiting Akt/mTOR and TNF-α/TNFR1 Signaling Pathways to Alleviate Pyroptosis and Necroptosis in Mycobacterium tuberculosis-Infected Macrophages
Inflammation (2023)
-
The concepts and origins of cell mortality
History and Philosophy of the Life Sciences (2023)
-
Hydrogen peroxide participated in programmed cell death by mediating ethylene during the cryopreservation of Dendrobium nobile protocorm-like bodies
Acta Physiologiae Plantarum (2023)
