Fas-Induced Necrosis

  • Tom Vanden Berghe
  • Nele Festjens
  • Michael Kalai
  • Xavier Saelens
  • Peter Vandenabeele
Part of the Medical Intelligence Unit book series (MIUN)


Fas/CD95 is an important regulator of cell death in development and homeostasis of the immune system. Apoptosis is the most frequently observed type of cell death induced by Fas. It is characterized by cell shrinkage and nuclear fragmentation, while organelles and the plasma membrane retain their integrity for a prolonged period. Intensive studies of apoptotic cell death led to the discovery of the involvement of caspases. The first reports on necrotic caspase-independent cell death induced by Fas appeared in the late nineties. Necrotic cell death is characterized by minor nuclear changes and swelling of the cell, resulting in plasma and organelle membrane rupture. The current review focuses on Fas-initiated signaling events that allow a switch between apoptotic and necrotic cell death and on the mitochondrial processes that regulate an apoptotic or necrotic outcome. Finally, we describe events that are crucial for the execution of the necrotic cell death process.


Jurkat Cell Mitochondrial Permeability Transition Death Domain Necrotic Cell Death Cell Death Differ 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Abrahamse SL, van Runnard Heimel P, Hartman RJ et al. Induction of necrosis and DNA fragmentation during hypothermic preservation of hepatocytes in UW, HTK, and Celsior solutions. Cell Transplant 2003; 12:59–68.PubMedGoogle Scholar
  2. 2.
    Adams JM, Cory S. Life-or-death decisions by the Bcl-2 protein family. Trends Biochem Sci 2001; 26:61–6.PubMedGoogle Scholar
  3. 3.
    Adler V, Yin Z, Tew KD et al. Role of redox potential and reactive oxygen species in stress signaling. Oncogene 1999; 18:6104–11.PubMedGoogle Scholar
  4. 4.
    Algeciras-Schimnich A, Shen L, Barnhart BC et al. Molecular ordering of the initial signaling events of CD95. Mol Cell Biol 2002; 22:207–20.PubMedGoogle Scholar
  5. 5.
    Atsumi G, Tajima M, Hadano A et al. Fas-induced arachidonic acid release is mediated by Ca2+-independent phospholipase A2 but not cytosolic phospholipase A2, which undergoes proteolytic inactivation. J Biol Chem 1998; 273:13870–7.PubMedGoogle Scholar
  6. 6.
    Balsinde J, Dennis EA. Distinct roles in signal transduction for each of the phospholipase A2 enzymes present in P388D1 macrophages. J Biol Chem 1996; 271:6758–65.PubMedGoogle Scholar
  7. 7.
    Barja G. Mitochondrial oxygen radical generation and leak: Sites of production in states 4 and 3, organ specificity, and relation to aging and longevity. J Bioenerg Biomembr 1999; 31:347–66.PubMedGoogle Scholar
  8. 8.
    Barja G, Herrero A. Localization at complex I and mechanism of the higher free radical production of brain nonsynaptic mitochondria in the short-lived rat than in the longevous pigeon. J Bioenerg Biomembr 1998; 30:235–43.PubMedGoogle Scholar
  9. 9.
    Basnakian AG, Ueda N, Kaushal GP et al. DNase I-like endonuclease in rat kidney cortex that is activated during ischemia/reperfusion injury. J Am Soc Nephrol 2002; 13:1000–7.PubMedGoogle Scholar
  10. 10.
    Boldin MP, Goncharov TM, Goltsev YV et al. Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1-and TNF receptor-induced cell death. Cell 1996; 85:803–15.PubMedGoogle Scholar
  11. 11.
    Bonaldi T, Langst G, Strohner R et al. The DNA chaperone HMGB1 facilitates ACF/CHRAC-dependent nucleosome sliding. Embo J 2002; 21:6865–73.PubMedGoogle Scholar
  12. 12.
    Boone E, Vanden Berghe T, van Loo G et al. Structure/Function analysis of p55 tumor necrosis factor receptor and fas-associated death domain. Effect on necrosis in L929sA cells. J Biol Chem 2000; 275:37596–603.PubMedGoogle Scholar
  13. 13.
    Boya P, Andreau K, Poncet D et al. Lysosomal membrane permeabilization induces cell death in a mitochondrion-dependent fashion. J Exp Med 2003; 197:1323–34.PubMedGoogle Scholar
  14. 14.
    Brunk UT, Terman A. The mitochondrial-lysosomal axis theory of aging: Accumulation of damaged mitochondria as a result of imperfect autophagocytosis. Eur J Biochem 2002; 269:1996–2002.PubMedGoogle Scholar
  15. 15.
    Chautan M, Chazal G, Cecconi F et al. Interdigital cell death can occur through a necrotic and caspase-independent pathway. Curr Biol 1999; 9:967–70.PubMedGoogle Scholar
  16. 16.
    Chinnaiyan AM, Tepper CG, Seldin MF et al. FADD/MORTl is a common mediator of CD95 (Fas/APO-1) and tumor necrosis factor receptor-induced apoptosis. J Biol Chem 1996; 271:4961–5.PubMedGoogle Scholar
  17. 17.
    Clarke PG. Developmental cell death: Morphological diversity and multiple mechanisms. Anat Embryol (Berl) 1990; 181:195–213.PubMedGoogle Scholar
  18. 18.
    Clarke PG. Apoptosis: From morphological types of cell death to interacting pathways. Trends Pharmacol Sci 2002; 23:308–9.PubMedGoogle Scholar
  19. 19.
    Cory S, Adams JM. The Bcl2 family: Regulators of the cellular life-or-death switch. Nat Rev Cancer 2002; 2:647–56.PubMedGoogle Scholar
  20. 20.
    Cremesti A, Paris F, Grassme H et al. Ceramide enables fas to cap and kill. J Biol Chem 2001; 276:23954–61.PubMedGoogle Scholar
  21. 21.
    Crompton M. The mitochondrial permeability transition pore and its role in cell death. Biochem J 1999; 341(Pt2):233–49.PubMedGoogle Scholar
  22. 22.
    Cummings BS, McHowat J, Schnellmann RG. Phospholipase A(2)s in cell injury and death. J Pharmacol Exp Ther 2000; 294:793–9.PubMedGoogle Scholar
  23. 23.
    De Valck D, Vercammen D, Fiers W et al. Differential activation of phospholipases during necrosis or apoptosis: A comparative study using tumor necrosis factor and anti-Fas antibodies. J Cell Biochem 1998; 71:392–9.PubMedGoogle Scholar
  24. 24.
    Denecker G, Vercammen D, Steemans M et al. Death receptor-induced apoptotic and necrotic cell death: Differential role of caspases and mitochondria. Cell Death Differ 2001; 8:829–40.PubMedGoogle Scholar
  25. 25.
    Donepudi M, Mac Sweeney A, Briand C et al. Insights into the regulatory mechanism for caspase-8 activation. Mol Cell 2003; 11:543–9.PubMedGoogle Scholar
  26. 26.
    Eguchi Y, Shimizu S, Tsujimoto Y. Intracellular ATP levels determine cell death fate by apoptosis or necrosis. Cancer Res 1997; 57:1835–40.PubMedGoogle Scholar
  27. 27.
    Eguchi Y, Srinivasan A, Tomaselli KJ et al. ATP-dependent steps in apoptotic signal transduction. Cancer Res 1999; 59:2174–81.PubMedGoogle Scholar
  28. 28.
    Enari M, Hug H, Hayakawa M et al. Different apoptotic pathways mediated by Fas and the tumor-necrosis-factor receptor. Cytosolic phospholipase A2 is not involved in Fas-mediated apoptosis. Eur J Biochem 1996; 236:533–8.PubMedGoogle Scholar
  29. 29.
    Enari M, Hug H, Nagata S. Involvement of an ICE-like protease in Fas-mediated apoptosis. Nature 1995; 375:78–81.PubMedGoogle Scholar
  30. 30.
    Ferrari D, Stepczynska A, Los M et al. Differential regulation and ATP requirement for caspase-8 and caspase-3 activation during CD95-and anticancer drug-induced apoptosis. J Exp Med 1998; 188:979–84.PubMedGoogle Scholar
  31. 31.
    Festjens N, Van Gurp M, van Loo G et al. Bcl-2 family members as sentinels of cellular integrity and role of mitochondrial intermembrane space proteins in apoptotic cell death. Acta Haematol 2004; 111:7–27.PubMedGoogle Scholar
  32. 32.
    Foghsgaard L, Wissing D, Mauch D et al. Cathepsin B acts as a dominant execution protease in tumor cell apoptosis induced by tumor necrosis factor. J Cell Biol 2001; 153:999–1010.PubMedGoogle Scholar
  33. 33.
    Goossens V, Grooten J, De Vos K et al. Direct evidence for tumor necrosis factor-induced mitochondrial reactive oxygen intermediates and their involvement in cytotoxicity. Proc Natl Acad Sci USA 1995; 92:8115–9.PubMedGoogle Scholar
  34. 34.
    Grassme H, Jekle A, Riehle A et al. CD95 signaling via ceramide-rich membrane rafts. J Biol Chem 2001; 276:20589–96.PubMedGoogle Scholar
  35. 35.
    Gunther T, Vormann J. Intracellular Ca(2+)-Mg2+ interactions. Ren Physiol Biochem 1994; 17:279–86.PubMedGoogle Scholar
  36. 36.
    Guo K, Searfoss G, Krolikowski D et al. Hypoxia induces the expression of the pro-apoptotic gene BNIP3. Cell Death Differ 2001; 8:367–76.PubMedGoogle Scholar
  37. 37.
    Ha HC, Snyder SH. Poly(ADP-ribose) polymerase is a mediator of necrotic cell death by ATP depletion. Proc Natl Acad Sci USA 1999; 96:13978–82.PubMedGoogle Scholar
  38. 38.
    Han D, Williams E, Cadenas E. Mitochondrial respiratory chain-dependent generation of superoxide anion and its release into the intermembrane space. Biochem J 2001; 353:411–6.PubMedGoogle Scholar
  39. 39.
    Harper N, Hughes M, MacFarlane M et al. Fas-associated death domain protein and caspase-8 are not recruited to the tumor necrosis factor receptor 1 signaling complex during tumor necrosis factor-induced apoptosis. J Biol Chem 2003; 278:25534–41.PubMedGoogle Scholar
  40. 40.
    Hasegawa J, Kamada S, Kamiike W et al. Involvement of CPP32/Yama(-like) proteases in Fas-mediated apoptosis. Cancer Res 1996; 56:1713–8.PubMedGoogle Scholar
  41. 41.
    Herceg Z, Wang ZQ. Failure of poly(ADP-ribose) polymerase cleavage by caspases leads to induction of necrosis and enhanced apoptosis. Mol Cell Biol 1999; 19:5124–33.PubMedGoogle Scholar
  42. 42.
    Hetz CA, Hunn M, Rojas P et al. Caspase-dependent initiation of apoptosis and necrosis by the Fas receptor in lymphoid cells: Onset of necrosis is associated with delayed ceramide increase. J Cell Sci 2002; 115:4671–83.PubMedGoogle Scholar
  43. 43.
    Heyninck K, Denecker G, De Valck D et al. Inhibition of tumor necrosis factor-induced necrotic cell death by the zinc finger protein A20. Anticancer Res 1999; 19:2863–8.PubMedGoogle Scholar
  44. 44.
    Higuchi Y. Chromosomal DNA fragmentation in apoptosis and necrosis induced by oxidative stress. Biochem Pharmacol 2003; 66:1527–35.PubMedGoogle Scholar
  45. 45.
    Hill JM, Morisawa G, Kim T et al. Identification of an expanded binding surface on the FADD death domain responsible for interaction with CD95/Fas. J Biol Chem 2003.Google Scholar
  46. 46.
    Holler N, Zaru R, Micheau O et al. Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat Immunol 2000; 1:489–95.PubMedGoogle Scholar
  47. 47.
    Hsu H, Huang J, Shu HB et al. TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex. Immunity 1996; 4:387–96.PubMedGoogle Scholar
  48. 48.
    Huang DC, Hahne M, Schroeter M et al. Activation of Fas by FasL induces apoptosis by a mechanism that cannot be blocked by Bcl-2 or Bcl-x(L). Proc Natl Acad Sci USA 1999; 96:14871–6.PubMedGoogle Scholar
  49. 49.
    Hueber AO, Bernard AM, Herincs Z et al. An essential role for membrane rafts in the initiation of Fas/CD95-triggered cell death in mouse thymocytes. EMBO Rep 2002; 3:190–6.PubMedGoogle Scholar
  50. 50.
    Ichas F, Jouaville LS, Mazat JP. Mitochondria are excitable organelles capable of generating and conveying electrical and calcium signals. Cell 1997; 89:1145–53.PubMedGoogle Scholar
  51. 51.
    Itoh N, Nagata S. A novel protein domain required for apoptosis. Mutational analysis of human Fas antigen. J Biol Chem 1993; 268:10932–7.PubMedGoogle Scholar
  52. 52.
    Itoh N, Yonehara S, Ishii A et al. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 1991; 66:233–43.PubMedGoogle Scholar
  53. 53.
    Jayanthi S, Ordonez S, McCoy MT et al. Dual mechanism of Fas-induced cell death in neuroglioma cells: A role for reactive oxygen species. Brain Res Mol Brain Res 1999; 72:158–65.PubMedGoogle Scholar
  54. 54.
    Kalai M, Van Loo G, Vanden Berghe T et al. Tipping the balance between necrosis and apoptosis in human and murine cells treated with interferon and dsRNA. Cell Death Differ 2002; 9:981–94.PubMedGoogle Scholar
  55. 55.
    Kalra J, Lautner D, Massey KL et al. Oxygen free radicals induced release of lysosomal enzymes in vitro. Mol Cell Biochem 1988; 84:233–8.PubMedGoogle Scholar
  56. 56.
    Kawahara A, Ohsawa Y, Matsumura H et al. Caspase-independent cell killing by Fas-associated protein with death domain. J Cell Biol 1998; 143:1353–60.PubMedGoogle Scholar
  57. 57.
    Kawane K, Fukuyama H, Yoshida H et al. Impaired thymic development in mouse embryos deficient in apoptotic DNA degradation. Nat Immunol 2003; 4:138–44.PubMedGoogle Scholar
  58. 58.
    Khwaja A, Tatton L. Resistance to the cytotoxic effects of tumor necrosis factor alpha can be overcome by inhibition of a FADD/caspase-dependent signaling pathway. J Biol Chem 1999; 274:36817–23.PubMedGoogle Scholar
  59. 59.
    Kim JS, He L, Lemasters JJ. Mitochondrial permeability transition: A common pathway to necrosis and apoptosis. Biochem Biophys Res Commun 2003a; 304:463–70.PubMedGoogle Scholar
  60. 60.
    Kim JS, Qian T, Lemasters JJ. Mitochondrial permeability transition in the switch from necrotic to apoptotic cell death in ischemic rat hepatocytes. Gastroenterology 2003b; 124:494–503.PubMedGoogle Scholar
  61. 61.
    Kim JW, Choi EJ, Joe CO. Activation of death-inducing signaling complex (DISC) by pro-apoptotic C-terminal fragment of RIP. Oncogene 2000; 19:4491–9.PubMedGoogle Scholar
  62. 62.
    Kischkel FC, Hellbardt S, Behrmann I et al. Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. Embo J 1995; 14:5579–88.PubMedGoogle Scholar
  63. 63.
    Kohjimoto Y, Kennington L, Scheid CR et al. Role of phospholipase A2 in the cytotoxic effects of oxalate in cultured renal epithelial cells. Kidney Int 1999; 56:1432–41.PubMedGoogle Scholar
  64. 64.
    Korshunov SS, Skulachev VP, Starkov AA. High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria. FEBS Lett 1997; 416:15–8.PubMedGoogle Scholar
  65. 65.
    Kothari S, Cizeau J, McMillan-Ward E et al. BNIP3 plays a role in hypoxic cell death in human epithelial cells that is inhibited by growth factors EGF and IGF. Oncogene 2003; 22:4734–44.PubMedGoogle Scholar
  66. 66.
    Kowaltowski AJ, Castilho RF, Vercesi AE. Mitochondrial permeability transition and oxidative stress. FEBS Lett 2001; 495:12–5.PubMedGoogle Scholar
  67. 67.
    Kubasiak LA, Hernandez OM, Bishopric NH et al. Hypoxia and acidosis activate cardiac myocyte death through the Bcl-2 family protein BNIP3. Proc Natl Acad Sci USA 2002; 99:12825–30.PubMedGoogle Scholar
  68. 68.
    Lacronique V, Mignon A, Fabre M et al. Bcl-2 protects from lethal hepatic apoptosis induced by an anti-Fas antibody in mice. Nat Med 1996; 2:80–6.PubMedGoogle Scholar
  69. 69.
    Lamkanfi M, Declercq W, Depuydt B et al. The caspase family. In: Los M, Walczak H, eds. Caspases: Their Role in Cell Death and Cell Survival. Georgetown, TX: Landes Bioscience, Kluwer Academic Press, 2003.Google Scholar
  70. 70.
    Lamy L, Ticchioni M, Rouquette-Jazdanian AK et al. CD47 and the 19 kDa interacting protein-3 (BNIP3) in T cell apoptosis. J Biol Chem 2003; 278:23915–21.PubMedGoogle Scholar
  71. 71.
    Lardot C, Broeckaert F, Lison D et al. Exogenous catalase may potentiate oxidant-mediated lung injury in the female Sprague-Dawley rat. J Toxicol Environ Health 1996; 47:509–22.PubMedGoogle Scholar
  72. 72.
    Latta M, Kunstle G, Leist M et al. Metabolic depletion of ATP by fructose inversely controls CD95-and tumor necrosis factor receptor 1-mediated hepatic apoptosis. J Exp Med 2000; 191:1975–85.PubMedGoogle Scholar
  73. 73.
    Legembre P, Moreau P, Daburon S et al. Potentiation of Fas-mediated apoptosis by an engineered glycosylphosphatidylinositol-linked Fas. Cell Death Differ 2002; 9:329–39.PubMedGoogle Scholar
  74. 74.
    Leist M, Nicotera P. The shape of cell death. Biochem Biophys Res Commun 1997; 236:1–9.PubMedGoogle Scholar
  75. 75.
    Leist M, Single B, Naumann H et al. Nitric oxide inhibits execution of apoptosis at two distinct ATP-dependent steps upstream and downstream of mitochondrial cytochrome c release. Biochem Biophys Res Commun 1999; 258:215–21.PubMedGoogle Scholar
  76. 76.
    Lewis J, Devin A, Miller A et al. Disruption of hsp90 function results in degradation of the death domain kinase, receptor-interacting protein (RIP), and blockage of tumor necrosis factor-induced nuclear factor-kappaB activation. J Biol Chem 2000; 275:10519–26.PubMedGoogle Scholar
  77. 77.
    Li H, Zhu H, Xu CJ et al. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 1998; 94:491–501.PubMedGoogle Scholar
  78. 78.
    Li P, Nijhawan D, Budihardjo I et al. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 1997; 91:479–89.PubMedGoogle Scholar
  79. 79.
    Li W, Yuan X, Nordgren G et al. Induction of cell death by the lysosomotropic detergent MSDH. FEBS Lett 2000; 470:35–9.PubMedGoogle Scholar
  80. 80.
    Lin Y, Devin A, Rodriguez Y et al. Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced apoptosis. Genes Dev 1999; 13:2514–26.PubMedGoogle Scholar
  81. 81.
    Lockshin RA, Williams CM. Programmed cell death. II. Endocrine potentiation of the breakdown of the intersegmental muscles of silkmoths. J. Insect Physiol 1964; 10:643–649.Google Scholar
  82. 82.
    Los M, Mozoluk M, Ferrari D et al. Activation and caspase-mediated inhibition of PARP: A molecular switch between fibroblast necrosis and apoptosis in death receptor signaling. Mol Biol Cell 2002; 13:978–88.PubMedGoogle Scholar
  83. 83.
    Los M, Van de Craen M, Penning LC et al. Requirement of an ICE/CED-3 protease for Fas/APO-1-mediated apoptosis. Nature 1995; 375:81–3.PubMedGoogle Scholar
  84. 84.
    Martinon F, Holler N, Richard C et al. Activation of a pro-apoptotic amplification loop through inhibition of NF-kappaB-dependent survival signals by caspase-mediated inactivation of RIP. FEBS Lett 2000; 468:134–6.PubMedGoogle Scholar
  85. 85.
    Mateo V, Lagneaux L, Bron D et al. CD47 ligation induces caspase-independent cell death in chronic lymphocytic leukemia. Nat Med 1999; 5:1277–84.PubMedGoogle Scholar
  86. 86.
    Meilhac O, Escargueil-Blanc I, Thiers JC et al. Bcl-2 alters the balance between apoptosis and necrosis, but does not prevent cell death induced by oxidized low density lipoproteins. Faseb J 1999; 13:485–94.PubMedGoogle Scholar
  87. 87.
    Memon SA, Moreno MB, Petrak D et al. Bcl-2 blocks glucocorticoid-but not Fas-or activation-induced apoptosis in a T cell hybridoma. J Immunol 1995; 155:4644–52.PubMedGoogle Scholar
  88. 88.
    Micheau O, Tschopp J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell 2003; 114:181–90.PubMedGoogle Scholar
  89. 89.
    Mohr S, Zech B, Lapetina EG et al. Inhibition of caspase-3 by S-nitrosation and oxidation caused by nitric oxide. Biochem Biophys Res Commun 1997; 238:387–91.PubMedGoogle Scholar
  90. 90.
    Morel Y, Barouki R. Repression of gene expression by oxidative stress. Biochem J 1999; 342 (Pt 3):481–96.PubMedGoogle Scholar
  91. 91.
    Muller S, Scaffidi P, Degryse B et al. New EMBO members’ review: The double life of HMGB1 chromatin protein: Architectural factor and extracellular signal. Embo J 2001; 20:4337–40.PubMedGoogle Scholar
  92. 92.
    Murakami M, Kudo I. Phospholipase A2. J Biochem (Tokyo) 2002; 131:285–92.PubMedGoogle Scholar
  93. 93.
    Muzio M, Chinnaiyan AM, Kischkel FC 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; 85:817–27.PubMedGoogle Scholar
  94. 94.
    Nakayama M, Ishidoh K, Kayagaki N et al. Multiple pathways of TWEAK-induced cell death. J Immunol 2002; 168:734–43.PubMedGoogle Scholar
  95. 95.
    Napirei M, Wulf S, Mannherz HG. Chromatin breakdown during necrosis by serum Dnase1 and the plasminogen system. Arthritis & Rheumatism 2004; In press.Google Scholar
  96. 96.
    Ollinger K, Brunk UT. Cellular injury induced by oxidative stress is mediated through lysosomal damage. Free Radic Biol Med 1995; 19:565–74.PubMedGoogle Scholar
  97. 97.
    Orrenius S, Zhivotovsky B, Nicotera P. Regulation of cell death: The calcium-apoptosis link. Nat Rev Mol Cell Biol 2003; 4:552–65.PubMedGoogle Scholar
  98. 98.
    Papoff G, Hausler P, Eramo A et al. Identification and characterization of a ligand-independent oligomerization domain in the extracellular region of the CD95 death receptor. J Biol Chem 1999; 274:38241–50.PubMedGoogle Scholar
  99. 99.
    Peter ME, Krammer PH. The CD95(APO-1/Fas) DISC and beyond. Cell Death Differ 2003; 10:26–35.PubMedGoogle Scholar
  100. 100.
    Raymond MA, Mollica L, Vigneault N et al. Blockade of the apoptotic machinery by cyclosporin A redirects cell death toward necrosis in arterial endothelial cells: Regulation by reactive oxygen species and cathepsin D. Faseb J 2003; 17:515–7.PubMedGoogle Scholar
  101. 101.
    Rizzuto R, Pinton P, Ferrari D et al. Calcium and apoptosis: Facts and hypotheses. Oncogene 2003; 22:8619–27.PubMedGoogle Scholar
  102. 102.
    Sapirstein A, Spech RA, Witzgall R et al. Cytosolic phospholipase A2 (PLA2), but not secretory PLA2, potentiates hydrogen peroxide cytotoxicity in kidney epithelial cells. J Biol Chem 1996; 271:21505–13.PubMedGoogle Scholar
  103. 103.
    Scaffidi C, Fulda S, Srinivasan A et al. Two CD95 (APO-1/Fas) signaling pathways. Embo J 1998; 17:1675–87.PubMedGoogle Scholar
  104. 104.
    Scaffidi C, Schmitz I, Zha J et al. Differential modulation of apoptosis sensitivity in CD95 type I and type II cells. J Biol Chem 1999; 274:22532–8.PubMedGoogle Scholar
  105. 105.
    Scaffidi P, Misteli T, Bianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 2002; 418:191–5.PubMedGoogle Scholar
  106. 106.
    Schulze-Osthoff K, Beyaert R, Vandevoorde V et al. Depletion of the mitochondrial electron transport abrogates the cytotoxic and gene-inductive effects of TNF. Embo J 1993; 12:3095–104.PubMedGoogle Scholar
  107. 107.
    Schweichel JU, Merker HJ. The morphology of various types of cell death in prenatal tissues. Teratology 1973; 7:253–66.Google Scholar
  108. 108.
    Shinoura N, Yoshida Y, Asai A et al. Relative level of expression of Bax and Bcl-XL determines the cellular fate of apoptosis/necrosis induced by the overexpression of Bax. Oncogene 1999; 18:5703–13.PubMedGoogle Scholar
  109. 109.
    Siegel RM, Frederiksen JK, Zacharias DA et al. Fas preassociation required for apoptosis signaling and dominant inhibition by pathogenic mutations. Science 2000; 288:2354–7.PubMedGoogle Scholar
  110. 110.
    Smith CA, Farrah T, Goodwin RG. The TNF receptor superfamily of cellular and viral proteins: Activation, costimulation, and death. Cell 1994; 76:959–62.PubMedGoogle Scholar
  111. 111.
    Sowter HM, Ratcliffe PJ, Watson P et al. HIF-1-dependent regulation of hypoxic induction of the cell death factors BNIP3 and NIX in human tumors. Cancer Res 2001; 61:6669–73.PubMedGoogle Scholar
  112. 112.
    Spencer MJ, Croall DE, Tidball JG. Calpains are activated in necrotic fibers from mdx dystrophic mice. J Biol Chem 1995; 270:10909–14.PubMedGoogle Scholar
  113. 113.
    Spiteller G. Are lipid peroxidation processes induced by changes in the cell wall structure and how are these processes connected with diseases? Med Hypotheses 2003; 60:69–83.PubMedGoogle Scholar
  114. 114.
    Strasser A, Harris AW, Huang DC et al. Bcl-2 and Fas/APO-1 regulate distinct pathways to lymphocyte apoptosis. Embo J 1995; 14:6136–47.PubMedGoogle Scholar
  115. 115.
    Syntichaki P, Tavernarakis N. Death by necrosis. Uncontrollable catastrophe, or is there order behind the chaos? EMBO Rep 2002; 3:604–9.PubMedGoogle Scholar
  116. 116.
    Syntichaki P, Xu K, Driscoll M et al. Specific aspartyl and calpain proteases are required for neurodegeneration in C. elegans. Nature 2002; 419:939–44.PubMedGoogle Scholar
  117. 117.
    Tavernarakis N, Xu K, Driscoll M. Execution of necrotic-like cell death in caenorhabditis elegans requires cathepsin d activity. Scientific World Journal 2001; 1:139.Google Scholar
  118. 118.
    Tepper AD, Ruurs P, Wiedmer T et al. Sphingomyelin hydrolysis to ceramide during the execution phase of apoptosis results from phospholipid scrambling and alters cell-surface morphology. J Cell Biol 2000; 150:155–64.PubMedGoogle Scholar
  119. 119.
    Thomas LR, Stillman DJ, Thorburn A. Regulation of Fas-associated death domain interactions by the death effector domain identified by a modified reverse two-hybrid screen. J Biol Chem 2002; 277:34343–8.PubMedGoogle Scholar
  120. 120.
    Trauth BC, Klas C, Peters AM et al. Monoclonal antibody-mediated tumor regression by induction of apoptosis. Science 1989; 245:301–5.PubMedGoogle Scholar
  121. 121.
    Tsukada T Watanabe M, Yamashima T. Implications of CAD and DNase II in ischemic neuronal necrosis specific for the primate hippocampus. J Neurochem 2001; 79:1196–206.PubMedGoogle Scholar
  122. 122.
    Turpaev KT. Reactive oxygen species and regulation of gene expression. Biochemistry (Mosc) 2002; 67:281–92.PubMedGoogle Scholar
  123. 123.
    van Loo G, Saelens X, van Gurp M et al. The role of mitochondrial factors in apoptosis: A Russian roulette with more than one bullet. Cell Death Differ 2002; 9:1031–42.PubMedGoogle Scholar
  124. 124.
    Vande Velde C, Cizeau J, Dubik D et al. BNIP3 and genetic control of necrosis-like cell death through the mitochondrial permeability transition pore. Mol Cell Biol 2000; 20:5454–68.PubMedGoogle Scholar
  125. 125.
    Vanden Berghe T, Kalai M, van Loo G et al. Disruption of HSP90 function reverts tumor necrosis factor-induced necrosis to apoptosis. J Biol Chem 2003a; 278:5622–9.PubMedGoogle Scholar
  126. 126.
    Vanden Berghe T, van Loo G, Saelens X et al. Differential signaling to apoptotic and necrotic cell death by Fas-associated death domain protein FADD. J Biol Chem 2003b; in press.Google Scholar
  127. 127.
    Vander Heiden MG, Thompson CB. Bcl-2 proteins: Regulators of apoptosis or of mitochondrial homeostasis? Nat Cell Biol 1999; 1:E209–16.PubMedGoogle Scholar
  128. 128.
    Varfolomeev EE, Boldin MP, Goncharov TM et al. A potential mechanism of “cross-talk” between the p55 tumor necrosis factor receptor and Fas/APO1: Proteins binding to the death domains of the two receptors also bind to each other. J Exp Med 1996; 183:1271–5.PubMedGoogle Scholar
  129. 129.
    Vercammen D, Beyaert R, Denecker G et al. Inhibition of caspases increases the sensitivity of L929 cells to necrosis mediated by tumor necrosis factor. J Exp Med 1998a; 187:1477–85.PubMedGoogle Scholar
  130. 130.
    Vercammen D, Brouckaert G, Denecker G et al. Dual signaling of the Fas receptor: Initiation of both apoptotic and necrotic cell death pathways. J Exp Med 1998b; 188:919–30.PubMedGoogle Scholar
  131. 131.
    Virag L, Szabo C. The therapeutic potential of poly(ADP-ribose) polymerase inhibitors. Pharmacol Rev 2002; 54:375–429.PubMedGoogle Scholar
  132. 132.
    Wang KK. Calpain and caspase: Can you tell the difference? Trends Neurosci 2000; 23:20–6.PubMedGoogle Scholar
  133. 133.
    Wang X, Ryter SW, Dai C et al. Necrotic cell death in response to oxidant stress involves the activation of the apoptogenic caspase-8/bid pathway. J Biol Chem 2003; 278:29184–91.PubMedGoogle Scholar
  134. 134.
    Wang ZQ, Stingl L, Morrison C et al. PARP is important for genomic stability but dispensable in apoptosis. Genes Dev 1997; 11:2347–58.PubMedGoogle Scholar
  135. 135.
    Xu K, Tavernarakis N, Driscoll M. Necrotic cell death in C. elegans requires the function of calreticulin and regulators of Ca(2+) release from the endoplasmic reticulum. Neuron 2001; 31:957–71.PubMedGoogle Scholar
  136. 136.
    Yamashima T. Implication of cysteine proteases calpain, cathepsin and caspase in ischemic neuronal death of primates. Prog Neurobiol 2000; 62:273–95.PubMedGoogle Scholar
  137. 137.
    Yamashima T, Kohda Y, Tsuchiya K et al. Inhibition of ischaemic hippocampal neuronal death in primates with cathepsin B inhibitor CA-074: A novel strategy for neuroprotection based on ‘calpain-cathepsin hypothesis’. Eur J Neurosci 1998; 10:1723–33.PubMedGoogle Scholar
  138. 138.
    Yamashima T, Saido TC, Takita M et al. Transient brain ischaemia provokes Ca2+, PIP2 and calpain responses prior to delayed neuronal death in monkeys. Eur J Neurosci 1996; 8:1932–44.PubMedGoogle Scholar
  139. 139.
    Yamashima T, Tonchev AB, Tsukada T et al. Sustained calpain activation associated with lysosomal rupture executes necrosis of the postischemic CA1 neurons in primates. Hippocampus 2003; 13:791–800.PubMedGoogle Scholar
  140. 140.
    Yonehara S, Ishii A, Yonehara M. A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen codownregulated with the receptor of tumor necrosis factor. J Exp Med 1989; 169:1747–56.PubMedGoogle Scholar
  141. 141.
    Yu Z, Persson HL, Eaton JW et al. Intralysosomal iron: A major determinant of oxidant-induced cell death. Free Radic Biol Med 2003; 34:1243–52.PubMedGoogle Scholar
  142. 142.
    Zhang J, Liu X, Scherer DC et al. Resistance to DNA fragmentation and chromatin condensation in mice lacking the DNA fragmentation factor 45. Proc Natl Acad Sci USA 1998; 95:12480–5.PubMedGoogle Scholar
  143. 143.
    Zhao M, Antunes F, Eaton JW et al. Lysosomal enzymes promote mitochondrial oxidant production, cytochrome c release and apoptosis. Eur J Biochem 2003; 270:3778–86.PubMedGoogle Scholar
  144. 144.
    Zhu LP, Yu XD, Ling S et al. Mitochondrial Ca(2+)homeostasis in the regulation of apoptotic and necrotic cell deaths. Cell Calcium 2000; 28:107–17.PubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2006

Authors and Affiliations

  • Tom Vanden Berghe
    • 1
  • Nele Festjens
    • 2
  • Michael Kalai
    • 2
  • Xavier Saelens
    • 2
  • Peter Vandenabeele
    • 1
  1. 1.Department of Molecular Biology Flanders Interuniversity Institute for BiotechnologyUniversity of GentGentBelgium
  2. 2.Molecular Signalling and Cell Death Unit Department of Molecular Biology Flanders Interuniversity Institute for BiotechnologyUniversity of GentGentBelgium

Personalised recommendations