• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of embojLink to Publisher's site
EMBO J. Jan 2, 1998; 17(1): 37–49.
PMCID: PMC1170356

Mitochondrial cytochrome c release in apoptosis occurs upstream of DEVD-specific caspase activation and independently of mitochondrial transmembrane depolarization.

Abstract

Mitochondrial cytochrome c, which functions as an electron carrier in the respiratory chain, translocates to the cytosol in cells undergoing apoptosis, where it participates in the activation of DEVD-specific caspases. The apoptosis inhibitors Bcl-2 or Bcl-xL prevent the efflux of cytochrome c from mitochondria. The mechanism responsible for the release of cytochrome c from mitochondria during apoptosis is unknown. Here, we report that cytochrome c release from mitochondria is an early event in the apoptotic process induced by UVB irradiation or staurosporine treatment in CEM or HeLa cells, preceding or at the time of DEVD-specific caspase activation and substrate cleavage. A reduction in mitochondrial transmembrane potential (Deltapsim) occurred considerably later than cytochrome c translocation and caspase activation, and was not necessary for DNA fragmentation. Although zVAD-fmk substantially blocked caspase activity, a reduction in Deltapsim and cell death, it failed to prevent the passage of cytochrome c from mitochondria to the cytosol. Thus the translocation of cytochrome c from mitochondria to cytosol does not require a mitochondrial transmembrane depolarization.

Full Text

The Full Text of this article is available as a PDF (456K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Alnemri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornberry NA, Wong WW, Yuan J. Human ICE/CED-3 protease nomenclature. Cell. 1996 Oct 18;87(2):171–171. [PubMed]
  • Ankarcrona M, Dypbukt JM, Bonfoco E, Zhivotovsky B, Orrenius S, Lipton SA, Nicotera P. Glutamate-induced neuronal death: a succession of necrosis or apoptosis depending on mitochondrial function. Neuron. 1995 Oct;15(4):961–973. [PubMed]
  • Antonsson B, Conti F, Ciavatta A, Montessuit S, Lewis S, Martinou I, Bernasconi L, Bernard A, Mermod JJ, Mazzei G, et al. Inhibition of Bax channel-forming activity by Bcl-2. Science. 1997 Jul 18;277(5324):370–372. [PubMed]
  • Armstrong RC, Aja T, Xiang J, Gaur S, Krebs JF, Hoang K, Bai X, Korsmeyer SJ, Karanewsky DS, Fritz LC, et al. Fas-induced activation of the cell death-related protease CPP32 Is inhibited by Bcl-2 and by ICE family protease inhibitors. J Biol Chem. 1996 Jul 12;271(28):16850–16855. [PubMed]
  • Boise LH, Thompson CB. Bcl-x(L) can inhibit apoptosis in cells that have undergone Fas-induced protease activation. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3759–3764. [PMC free article] [PubMed]
  • Boldin MP, Goncharov TM, Goltsev YV, Wallach D. Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death. Cell. 1996 Jun 14;85(6):803–815. [PubMed]
  • Cardone MH, Salvesen GS, Widmann C, Johnson G, Frisch SM. The regulation of anoikis: MEKK-1 activation requires cleavage by caspases. Cell. 1997 Jul 25;90(2):315–323. [PubMed]
  • Casciola-Rosen L, Nicholson DW, Chong T, Rowan KR, Thornberry NA, Miller DK, Rosen A. Apopain/CPP32 cleaves proteins that are essential for cellular repair: a fundamental principle of apoptotic death. J Exp Med. 1996 May 1;183(5):1957–1964. [PMC free article] [PubMed]
  • Castedo M, Macho A, Zamzami N, Hirsch T, Marchetti P, Uriel J, Kroemer G. Mitochondrial perturbations define lymphocytes undergoing apoptotic depletion in vivo. Eur J Immunol. 1995 Dec;25(12):3277–3284. [PubMed]
  • Chinnaiyan AM, Dixit VM. The cell-death machine. Curr Biol. 1996 May 1;6(5):555–562. [PubMed]
  • Chinnaiyan AM, Orth K, O'Rourke K, Duan H, Poirier GG, Dixit VM. Molecular ordering of the cell death pathway. Bcl-2 and Bcl-xL function upstream of the CED-3-like apoptotic proteases. J Biol Chem. 1996 Mar 1;271(9):4573–4576. [PubMed]
  • Chinnaiyan AM, O'Rourke K, Lane BR, Dixit VM. Interaction of CED-4 with CED-3 and CED-9: a molecular framework for cell death. Science. 1997 Feb 21;275(5303):1122–1126. [PubMed]
  • Cossarizza A, Franceschi C, Monti D, Salvioli S, Bellesia E, Rivabene R, Biondo L, Rainaldi G, Tinari A, Malorni W. Protective effect of N-acetylcysteine in tumor necrosis factor-alpha-induced apoptosis in U937 cells: the role of mitochondria. Exp Cell Res. 1995 Sep;220(1):232–240. [PubMed]
  • Deckwerth TL, Johnson EM., Jr Temporal analysis of events associated with programmed cell death (apoptosis) of sympathetic neurons deprived of nerve growth factor. J Cell Biol. 1993 Dec;123(5):1207–1222. [PMC free article] [PubMed]
  • Drygas ME, Lambowitz AM, Nargang FE. Cloning and analysis of the Neurospora crassa gene for cytochrome c heme lyase. J Biol Chem. 1989 Oct 25;264(30):17897–17906. [PubMed]
  • Dumont ME, Ernst JF, Hampsey DM, Sherman F. Identification and sequence of the gene encoding cytochrome c heme lyase in the yeast Saccharomyces cerevisiae. EMBO J. 1987 Jan;6(1):235–241. [PMC free article] [PubMed]
  • Eguchi Y, Shimizu S, Tsujimoto Y. Intracellular ATP levels determine cell death fate by apoptosis or necrosis. Cancer Res. 1997 May 15;57(10):1835–1840. [PubMed]
  • Ellis RE, Yuan JY, Horvitz HR. Mechanisms and functions of cell death. Annu Rev Cell Biol. 1991;7:663–698. [PubMed]
  • Emoto Y, Manome Y, Meinhardt G, Kisaki H, Kharbanda S, Robertson M, Ghayur T, Wong WW, Kamen R, Weichselbaum R, et al. Proteolytic activation of protein kinase C delta by an ICE-like protease in apoptotic cells. EMBO J. 1995 Dec 15;14(24):6148–6156. [PMC free article] [PubMed]
  • Fraser A, Evan G. A license to kill. Cell. 1996 Jun 14;85(6):781–784. [PubMed]
  • Goldberg YP, Nicholson DW, Rasper DM, Kalchman MA, Koide HB, Graham RK, Bromm M, Kazemi-Esfarjani P, Thornberry NA, Vaillancourt JP, et al. Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract. Nat Genet. 1996 Aug;13(4):442–449. [PubMed]
  • Golstein P. Controlling cell death. Science. 1997 Feb 21;275(5303):1081–1082. [PubMed]
  • Hatefi Y. The mitochondrial electron transport and oxidative phosphorylation system. Annu Rev Biochem. 1985;54:1015–1069. [PubMed]
  • Hengartner MO, Horvitz HR. C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2. Cell. 1994 Feb 25;76(4):665–676. [PubMed]
  • Hengartner MO, Ellis RE, Horvitz HR. Caenorhabditis elegans gene ced-9 protects cells from programmed cell death. Nature. 1992 Apr 9;356(6369):494–499. [PubMed]
  • Henkart PA. ICE family proteases: mediators of all apoptotic cell death? Immunity. 1996 Mar;4(3):195–201. [PubMed]
  • Henkart PA, Grinstein S. Apoptosis: mitochondria resurrected? J Exp Med. 1996 Apr 1;183(4):1293–1295. [PMC free article] [PubMed]
  • Hennet T, Bertoni G, Richter C, Peterhans E. Expression of BCL-2 protein enhances the survival of mouse fibrosarcoid cells in tumor necrosis factor-mediated cytotoxicity. Cancer Res. 1993 Mar 15;53(6):1456–1460. [PubMed]
  • Hockenbery DM, Oltvai ZN, Yin XM, Milliman CL, Korsmeyer SJ. Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell. 1993 Oct 22;75(2):241–251. [PubMed]
  • Horvitz HR, Shaham S, Hengartner MO. The genetics of programmed cell death in the nematode Caenorhabditis elegans. Cold Spring Harb Symp Quant Biol. 1994;59:377–385. [PubMed]
  • Ichas F, Jouaville LS, Mazat JP. Mitochondria are excitable organelles capable of generating and conveying electrical and calcium signals. Cell. 1997 Jun 27;89(7):1145–1153. [PubMed]
  • Jacobson MD. Reactive oxygen species and programmed cell death. Trends Biochem Sci. 1996 Mar;21(3):83–86. [PubMed]
  • Jacobson MD, Burne JF, King MP, Miyashita T, Reed JC, Raff MC. Bcl-2 blocks apoptosis in cells lacking mitochondrial DNA. Nature. 1993 Jan 28;361(6410):365–369. [PubMed]
  • Jacobsen MD, Weil M, Raff MC. Role of Ced-3/ICE-family proteases in staurosporine-induced programmed cell death. J Cell Biol. 1996 Jun;133(5):1041–1051. [PMC free article] [PubMed]
  • Jacobson MD, Weil M, Raff MC. Programmed cell death in animal development. Cell. 1997 Feb 7;88(3):347–354. [PubMed]
  • James C, Gschmeissner S, Fraser A, Evan GI. CED-4 induces chromatin condensation in Schizosaccharomyces pombe and is inhibited by direct physical association with CED-9. Curr Biol. 1997 Apr 1;7(4):246–252. [PubMed]
  • Kantrow SP, Piantadosi CA. Release of cytochrome c from liver mitochondria during permeability transition. Biochem Biophys Res Commun. 1997 Mar 27;232(3):669–671. [PubMed]
  • Kass GE, Eriksson JE, Weis M, Orrenius S, Chow SC. Chromatin condensation during apoptosis requires ATP. Biochem J. 1996 Sep 15;318(Pt 3):749–752. [PMC free article] [PubMed]
  • Kerr JF. Shrinkage necrosis: a distinct mode of cellular death. J Pathol. 1971 Sep;105(1):13–20. [PubMed]
  • Kim CN, Wang X, Huang Y, Ibrado AM, Liu L, Fang G, Bhalla K. Overexpression of Bcl-X(L) inhibits Ara-C-induced mitochondrial loss of cytochrome c and other perturbations that activate the molecular cascade of apoptosis. Cancer Res. 1997 Aug 1;57(15):3115–3120. [PubMed]
  • Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD. The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science. 1997 Feb 21;275(5303):1132–1136. [PubMed]
  • Kluck RM, Martin SJ, Hoffman BM, Zhou JS, Green DR, Newmeyer DD. Cytochrome c activation of CPP32-like proteolysis plays a critical role in a Xenopus cell-free apoptosis system. EMBO J. 1997 Aug 1;16(15):4639–4649. [PMC free article] [PubMed]
  • Krippner A, Matsuno-Yagi A, Gottlieb RA, Babior BM. Loss of function of cytochrome c in Jurkat cells undergoing fas-mediated apoptosis. J Biol Chem. 1996 Aug 30;271(35):21629–21636. [PubMed]
  • Kroemer G. Mitochondrial implication in apoptosis. Towards an endosymbiont hypothesis of apoptosis evolution. Cell Death Differ. 1997 Aug;4(6):443–456. [PubMed]
  • Kroemer G. The proto-oncogene Bcl-2 and its role in regulating apoptosis. Nat Med. 1997 Jun;3(6):614–620. [PubMed]
  • Kroemer G, Zamzami N, Susin SA. Mitochondrial control of apoptosis. Immunol Today. 1997 Jan;18(1):44–51. [PubMed]
  • Kuida K, Zheng TS, Na S, Kuan C, Yang D, Karasuyama H, Rakic P, Flavell RA. Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice. Nature. 1996 Nov 28;384(6607):368–372. [PubMed]
  • Leist M, Single B, Castoldi AF, Kühnle S, Nicotera P. Intracellular adenosine triphosphate (ATP) concentration: a switch in the decision between apoptosis and necrosis. J Exp Med. 1997 Apr 21;185(8):1481–1486. [PMC free article] [PubMed]
  • Liu X, Kim CN, Yang J, Jemmerson R, Wang X. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell. 1996 Jul 12;86(1):147–157. [PubMed]
  • Liu X, Zou H, Slaughter C, Wang X. DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis. Cell. 1997 Apr 18;89(2):175–184. [PubMed]
  • Macho A, Decaudin D, Castedo M, Hirsch T, Susin SA, Zamzami N, Kroemer G. Chloromethyl-X-Rosamine is an aldehyde-fixable potential-sensitive fluorochrome for the detection of early apoptosis. Cytometry. 1996 Dec 1;25(4):333–340. [PubMed]
  • Marchetti P, Susin SA, Decaudin D, Gamen S, Castedo M, Hirsch T, Zamzami N, Naval J, Senik A, Kroemer G. Apoptosis-associated derangement of mitochondrial function in cells lacking mitochondrial DNA. Cancer Res. 1996 May 1;56(9):2033–2038. [PubMed]
  • Martin SJ, Green DR. Protease activation during apoptosis: death by a thousand cuts? Cell. 1995 Aug 11;82(3):349–352. [PubMed]
  • Martin SJ, Reutelingsperger CP, McGahon AJ, Rader JA, van Schie RC, LaFace DM, Green DR. Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J Exp Med. 1995 Nov 1;182(5):1545–1556. [PMC free article] [PubMed]
  • Mathews FS. The structure, function and evolution of cytochromes. Prog Biophys Mol Biol. 1985;45(1):1–56. [PubMed]
  • Minn AJ, Vélez P, Schendel SL, Liang H, Muchmore SW, Fesik SW, Fill M, Thompson CB. Bcl-x(L) forms an ion channel in synthetic lipid membranes. Nature. 1997 Jan 23;385(6614):353–357. [PubMed]
  • Miura M, Zhu H, Rotello R, Hartwieg EA, Yuan J. Induction of apoptosis in fibroblasts by IL-1 beta-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3. Cell. 1993 Nov 19;75(4):653–660. [PubMed]
  • Muchmore SW, Sattler M, Liang H, Meadows RP, Harlan JE, Yoon HS, Nettesheim D, Chang BS, Thompson CB, Wong SL, et al. X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death. Nature. 1996 May 23;381(6580):335–341. [PubMed]
  • Murphy AN, Bredesen DE, Cortopassi G, Wang E, Fiskum G. Bcl-2 potentiates the maximal calcium uptake capacity of neural cell mitochondria. Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9893–9898. [PMC free article] [PubMed]
  • Muzio M, Chinnaiyan AM, Kischkel FC, O'Rourke K, Shevchenko A, Ni J, Scaffidi C, Bretz JD, Zhang M, Gentz R, et al. FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death--inducing signaling complex. Cell. 1996 Jun 14;85(6):817–827. [PubMed]
  • Na S, Chuang TH, Cunningham A, Turi TG, Hanke JH, Bokoch GM, Danley DE. D4-GDI, a substrate of CPP32, is proteolyzed during Fas-induced apoptosis. J Biol Chem. 1996 May 10;271(19):11209–11213. [PubMed]
  • Nagata S. Apoptosis by death factor. Cell. 1997 Feb 7;88(3):355–365. [PubMed]
  • Newmeyer DD, Farschon DM, Reed JC. Cell-free apoptosis in Xenopus egg extracts: inhibition by Bcl-2 and requirement for an organelle fraction enriched in mitochondria. Cell. 1994 Oct 21;79(2):353–364. [PubMed]
  • Nicholson DW, Köhler H, Neupert W. Import of cytochrome c into mitochondria. Cytochrome c heme lyase. Eur J Biochem. 1987 Apr 1;164(1):147–157. [PubMed]
  • Nicholson DW, Ali A, Thornberry NA, Vaillancourt JP, Ding CK, Gallant M, Gareau Y, Griffin PR, Labelle M, Lazebnik YA, et al. Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature. 1995 Jul 6;376(6535):37–43. [PubMed]
  • Nicolli A, Basso E, Petronilli V, Wenger RM, Bernardi P. Interactions of cyclophilin with the mitochondrial inner membrane and regulation of the permeability transition pore, and cyclosporin A-sensitive channel. J Biol Chem. 1996 Jan 26;271(4):2185–2192. [PubMed]
  • Nicotera P, Leist M. Energy supply and the shape of death in neurons and lymphoid cells. Cell Death Differ. 1997 Aug;4(6):435–442. [PubMed]
  • Patel T, Gores GJ, Kaufmann SH. The role of proteases during apoptosis. FASEB J. 1996 Apr;10(5):587–597. [PubMed]
  • Petit PX, Lecoeur H, Zorn E, Dauguet C, Mignotte B, Gougeon ML. Alterations in mitochondrial structure and function are early events of dexamethasone-induced thymocyte apoptosis. J Cell Biol. 1995 Jul;130(1):157–167. [PMC free article] [PubMed]
  • Polla BS, Kantengwa S, François D, Salvioli S, Franceschi C, Marsac C, Cossarizza A. Mitochondria are selective targets for the protective effects of heat shock against oxidative injury. Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6458–6463. [PMC free article] [PubMed]
  • Reed JC. Double identity for proteins of the Bcl-2 family. Nature. 1997 Jun 19;387(6635):773–776. [PubMed]
  • Richter C, Schweizer M, Cossarizza A, Franceschi C. Control of apoptosis by the cellular ATP level. FEBS Lett. 1996 Jan 8;378(2):107–110. [PubMed]
  • Schendel SL, Xie Z, Montal MO, Matsuyama S, Montal M, Reed JC. Channel formation by antiapoptotic protein Bcl-2. Proc Natl Acad Sci U S A. 1997 May 13;94(10):5113–5118. [PMC free article] [PubMed]
  • Shimizu S, Eguchi Y, Kamiike W, Matsuda H, Tsujimoto Y. Bcl-2 expression prevents activation of the ICE protease cascade. Oncogene. 1996 Jun 6;12(11):2251–2257. [PubMed]
  • Shimizu S, Eguchi Y, Kamiike W, Waguri S, Uchiyama Y, Matsuda H, Tsujimoto Y. Bcl-2 blocks loss of mitochondrial membrane potential while ICE inhibitors act at a different step during inhibition of death induced by respiratory chain inhibitors. Oncogene. 1996 Jul 4;13(1):21–29. [PubMed]
  • Simonian NA, Coyle JT. Oxidative stress in neurodegenerative diseases. Annu Rev Pharmacol Toxicol. 1996;36:83–106. [PubMed]
  • Song Q, Lees-Miller SP, Kumar S, Zhang Z, Chan DW, Smith GC, Jackson SP, Alnemri ES, Litwack G, Khanna KK, et al. DNA-dependent protein kinase catalytic subunit: a target for an ICE-like protease in apoptosis. EMBO J. 1996 Jul 1;15(13):3238–3246. [PMC free article] [PubMed]
  • Spector MS, Desnoyers S, Hoeppner DJ, Hengartner MO. Interaction between the C. elegans cell-death regulators CED-9 and CED-4. Nature. 1997 Feb 13;385(6617):653–656. [PubMed]
  • Stuart RA, Neupert W. Apocytochrome c: an exceptional mitochondrial precursor protein using an exceptional import pathway. Biochimie. 1990 Feb-Mar;72(2-3):115–121. [PubMed]
  • Susin SA, Zamzami N, Castedo M, Hirsch T, Marchetti P, Macho A, Daugas E, Geuskens M, Kroemer G. Bcl-2 inhibits the mitochondrial release of an apoptogenic protease. J Exp Med. 1996 Oct 1;184(4):1331–1341. [PMC free article] [PubMed]
  • Susin SA, Zamzami N, Castedo M, Daugas E, Wang HG, Geley S, Fassy F, Reed JC, Kroemer G. The central executioner of apoptosis: multiple connections between protease activation and mitochondria in Fas/APO-1/CD95- and ceramide-induced apoptosis. J Exp Med. 1997 Jul 7;186(1):25–37. [PMC free article] [PubMed]
  • Tewari M, Quan LT, O'Rourke K, Desnoyers S, Zeng Z, Beidler DR, Poirier GG, Salvesen GS, Dixit VM. Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase. Cell. 1995 Jun 2;81(5):801–809. [PubMed]
  • Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science. 1995 Mar 10;267(5203):1456–1462. [PubMed]
  • Tropea F, Troiano L, Monti D, Lovato E, Malorni W, Rainaldi G, Mattana P, Viscomi G, Ingletti MC, Portolani M, et al. Sendai virus and herpes virus type 1 induce apoptosis in human peripheral blood mononuclear cells. Exp Cell Res. 1995 May;218(1):63–70. [PubMed]
  • Tsujimoto Y. Apoptosis and necrosis: intracellular ATP level as a determinant for cell death modes. Cell Death Differ. 1997 Aug;4(6):429–434. [PubMed]
  • Vaux DL. CED-4--the third horseman of apoptosis. Cell. 1997 Aug 8;90(3):389–390. [PubMed]
  • Vaux DL, Strasser A. The molecular biology of apoptosis. Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2239–2244. [PMC free article] [PubMed]
  • Vayssiere JL, Petit PX, Risler Y, Mignotte B. Commitment to apoptosis is associated with changes in mitochondrial biogenesis and activity in cell lines conditionally immortalized with simian virus 40. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11752–11756. [PMC free article] [PubMed]
  • Gajewski TF, Thompson CB. Apoptosis meets signal transduction: elimination of a BAD influence. Cell. 1996 Nov 15;87(4):589–592. [PubMed]
  • Wang X, Zelenski NG, Yang J, Sakai J, Brown MS, Goldstein JL. Cleavage of sterol regulatory element binding proteins (SREBPs) by CPP32 during apoptosis. EMBO J. 1996 Mar 1;15(5):1012–1020. [PMC free article] [PubMed]
  • Weil M, Jacobson MD, Coles HS, Davies TJ, Gardner RL, Raff KD, Raff MC. Constitutive expression of the machinery for programmed cell death. J Cell Biol. 1996 Jun;133(5):1053–1059. [PMC free article] [PubMed]
  • White E. Life, death, and the pursuit of apoptosis. Genes Dev. 1996 Jan 1;10(1):1–15. [PubMed]
  • Wu D, Wallen HD, Nuñez G. Interaction and regulation of subcellular localization of CED-4 by CED-9. Science. 1997 Feb 21;275(5303):1126–1129. [PubMed]
  • Wyllie AH, Kerr JF, Currie AR. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251–306. [PubMed]
  • Xue D, Shaham S, Horvitz HR. The Caenorhabditis elegans cell-death protein CED-3 is a cysteine protease with substrate specificities similar to those of the human CPP32 protease. Genes Dev. 1996 May 1;10(9):1073–1083. [PubMed]
  • Yang E, Korsmeyer SJ. Molecular thanatopsis: a discourse on the BCL2 family and cell death. Blood. 1996 Jul 15;88(2):386–401. [PubMed]
  • Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng TI, Jones DP, Wang X. Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science. 1997 Feb 21;275(5303):1129–1132. [PubMed]
  • Yuan J, Shaham S, Ledoux S, Ellis HM, Horvitz HR. The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme. Cell. 1993 Nov 19;75(4):641–652. [PubMed]
  • Zamzami N, Marchetti P, Castedo M, Decaudin D, Macho A, Hirsch T, Susin SA, Petit PX, Mignotte B, Kroemer G. Sequential reduction of mitochondrial transmembrane potential and generation of reactive oxygen species in early programmed cell death. J Exp Med. 1995 Aug 1;182(2):367–377. [PMC free article] [PubMed]
  • Zamzami N, Marchetti P, Castedo M, Zanin C, Vayssière JL, Petit PX, Kroemer G. Reduction in mitochondrial potential constitutes an early irreversible step of programmed lymphocyte death in vivo. J Exp Med. 1995 May 1;181(5):1661–1672. [PMC free article] [PubMed]
  • Zamzami N, Susin SA, Marchetti P, Hirsch T, Gómez-Monterrey I, Castedo M, Kroemer G. Mitochondrial control of nuclear apoptosis. J Exp Med. 1996 Apr 1;183(4):1533–1544. [PMC free article] [PubMed]
  • Zoratti M, Szabò I. The mitochondrial permeability transition. Biochim Biophys Acta. 1995 Jul 17;1241(2):139–176. [PubMed]
  • Zou H, Henzel WJ, Liu X, Lutschg A, Wang X. Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell. 1997 Aug 8;90(3):405–413. [PubMed]

Articles from The EMBO Journal are provided here courtesy of The European Molecular Biology Organization

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...