Control of mitochondrial integrity by Bcl-2 family members and caspase-independent cell death

Biochimica et Biophysica Acta - Molecular Cell Research

Volumn 1644, Issue 2-3, 2004, Pages 133-147

  Donovan, Maryanne ^a   Cotter, Thomas G ^a  

^a UNIVERSITY COLLEGE CORK   (Ireland)

Author keywords

AIF; Apoptosis; Bcl 2 family; Caspase independent; Mitochondrion

Indexed keywords

BIM PROTEIN; CASPASE; CASPASE 3; CYSTEINE PROTEINASE; FLAVOPROTEIN; PROTEIN; PROTEIN AIF; PROTEIN BAD; PROTEIN BAK; PROTEIN BAX; PROTEIN BCL 2; PROTEIN BCL W; PROTEIN BCL XL; PROTEIN BIK; PROTEIN ENDOG; PROTEIN NOXA; PROTEIN PUMA; PROTEIN SPIKE; SERINE PROTEINASE; SERINE PROTEINASE OMI; UNCLASSIFIED DRUG;

AMINO ACID SEQUENCE; APOPTOSIS; CELL STIMULATION; CELL STRUCTURE; CELL TYPE; CELL ULTRASTRUCTURE; CHANNEL GATING; COMPLEX FORMATION; ENZYME ACTIVATION; HOMEOSTASIS; HUMAN; MITOCHONDRIAL MEMBRANE; MITOCHONDRION; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN FAMILY; PROTEIN FUNCTION; REGULATORY MECHANISM; REVIEW; SEQUENCE ANALYSIS; SEQUENCE HOMOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; APOPTOSIS; APOPTOSIS INDUCING FACTOR; CASPASES; ENDODEOXYRIBONUCLEASES; FLAVOPROTEINS; HUMANS; INTRACELLULAR MEMBRANES; MEMBRANE PROTEINS; MEMBRANE TRANSPORT PROTEINS; MITOCHONDRIA; MITOCHONDRIAL PROTEINS; PERMEABILITY; PROTO-ONCOGENE PROTEINS C-BCL-2; SERINE ENDOPEPTIDASES;

EID: 1442310922     PISSN: 01674889     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bbamcr.2003.08.011     Document Type: Review

References (152)

1. Ellis H.M., Horvitz H.R. Genetic control of programmed cell death in the nematode C. elegans. Cell. 44:1986;817-829.
2. Ellis R.E., Yuan J.Y., Horvitz H.R. Mechanisms and functions of cell death. Annu. Rev. Cell Biol. 7:1991;663-698.
3. Yuan J., Shaham S., Ledoux S., Ellis H.M., Horvitz H.R. The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme. Cell. 75:1993;641-652.
4. Richardson H., Kumar S. Death to flies: Drosophila as a model system to study programmed cell death. J. Immunol. Methods. 265:2002;21-38.
5. Song Z., McCall K., Steller H. DCP-1, a Drosophila cell death protease essential for development. Science. 275:1997;536-540.
6. Salvesen G.S., Duckett C.S. IAP proteins: blocking the road to death's door. Nat. Rev., Mol. Cell Biol. 3:2002;401-410.
7. Stennicke H.R., Ryan C.A., Salvesen G.S. Reprieval from execution: the molecular basis of caspase inhibition. Trends Biochem. Sci. 27:2002;94-101.
8. Morishima N., Nakanishi K., Takenouchi H., Shibata T., Yasuhiko Y. An endoplasmic reticulum stress-specific caspase cascade in apoptosis. Cytochrome c-independent activation of caspase-9 by caspase-12. J. Biol. Chem. 277:2002;34287-34294.
9. Rudner J., Jendrossek V., Belka C. New insights in the role of Bcl-2 and the endoplasmic reticulum. Apoptosis. 7:2002;441-447.
10. Doonan F., Donovan M., Cotter T.G. Caspase-independent photoreceptor apoptosis in mouse models of retinal degeneration. J. Neurosci. 23:2003;5723-5731.
11. Donovan M., Cotter T.G. Caspase-independent photoreceptor apoptosis in vivo and differential expression of apoptotic protease activating factor-1 and caspase-3 during retinal development. Cell Death Differ. 9:2002;1220-1231.
12. Fraser A., James C. Fermenting debate: do yeast undergo apoptosis? Trends Cell Biol. 8:1998;219-221.
13. Madeo F., Frohlich E., Frohlich K.U. A yeast mutant showing diagnostic markers of early and late apoptosis. J. Cell Biol. 139:1997;729-734.
14. Borner C. The Bcl-2 protein family: sensors and checkpoints for life-or-death decisions. Mol. Immunol. 39:2003;615-647.
15. Shirane M., Nakayama K.I. Inherent calcineurin inhibitor FKBP38 targets Bcl-2 to mitochondria and inhibits apoptosis. Nat. Cell Biol. 5:2003;28-37.
16. Tsujimoto Y., Shimizu S. The voltage-dependent anion channel: an essential player in apoptosis. Biochimie. 84:2002;187-193.
17. Antonsson B. Bax and other pro-apoptotic Bcl-2 family "killer-proteins" and their victim the mitochondrion. Cell Tissue Res. 306:2001;347-361.
18. Zamzami N., Kroemer G. The mitochondrion in apoptosis: how Pandora's box opens. Nat. Rev. Mol. Cell Biol. 2:2001;67-71.
19. Martinou J.C., Green D.R. Breaking the mitochondrial barrier. Nat. Rev., Mol. Cell Biol. 2:2001;63-67.
20. Muchmore S.W., Sattler M., Liang H., Meadows R.P., Harlan J.E., Yoon H.S., Nettesheim D., Chang B.S., Thompson C.B., Wong S.L., Ng S.L., Fesik S.W. X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death. Nature. 381:1996;335-341.
21. Antonsson B., Conti F., Ciavatta A., Montessuit S., Lewis S., Martinou I., Bernasconi L., Bernard A., Mermod J.J., Mazzei G., Maundrell K., Gambale F., Sadoul R., Martinou J.C. Inhibition of Bax channel-forming activity by Bcl-2. Science. 277:1997;370-372.
22. Schlesinger P.H., Gross A., Yin X.M., Yamamoto K., Saito M., Waksman G., Korsmeyer S.J. Comparison of the ion channel characteristics of proapoptotic BAX and antiapoptotic BCL-2. Proc. Natl. Acad. Sci. U. S. A. 94:1997;11357-11362.
23. Schendel S.L., Xie Z., Montal M.O., Matsuyama S., Montal M., Reed J.C. Channel formation by antiapoptotic protein Bcl-2. Proc. Natl. Acad. Sci. U. S. A. 94:1997;5113-5118.
24. Minn A.J., Velez P., Schendel S.L., Liang H., Muchmore S.W., Fesik S.W., Fill M., Thompson C.B. Bcl-x(L) forms an ion channel in synthetic lipid membranes. Nature. 385:1997;353-357.
25. Schendel S.L., Azimov R., Pawlowski K., Godzik A., Kagan B.L., Reed J.C. Ion channel activity of the BH3 only Bcl-2 family member, BID. J. Biol. Chem. 274:1999;21932-21936.
26. Hsu Y.T., Wolter K.G., Youle R.J. Cytosol-to-membrane redistribution of Bax and Bcl-X(L) during apoptosis. Proc. Natl. Acad. Sci. U. S. A. 94:1997;3668-3672.
27. Gross A., Jockel J., Wei M.C., Korsmeyer S.J. Enforced dimerization of BAX results in its translocation, mitochondrial dysfunction and apoptosis. EMBO J. 17:1998;3878-3885.
28. Murphy K.M., Streips U.N., Lock R.B. Bcl-2 inhibits a Fas-induced conformational change in the Bax N terminus and Bax mitochondrial translocation. J. Biol. Chem. 275:2000;17225-17228.
29. Nechushtan A., Smith C.L., Hsu Y.T., Youle R.J. Conformation of the Bax C-terminus regulates subcellular location and cell death. EMBO J. 18:1999;2330-2341.
30. Wood D.E., Newcomb E.W. Cleavage of Bax enhances its cell death function. Exp. Cell Res. 256:2000;375-382.
31. Gao G., Dou Q.P. N-terminal cleavage of bax by calpain generates a potent proapoptotic 18-kDa fragment that promotes bcl-2-independent cytochrome C release and apoptotic cell death. J. Cell. Biochem. 80:2000;53-72.
32. Antonsson B., Montessuit S., Lauper S., Eskes R., Martinou J.C. Bax oligomerization is required for channel-forming activity in liposomes and to trigger cytochrome c release from mitochondria. Biochem. J. 345(Pt 2):2000;271-278.
33. Mikhailov V., Mikhailova M., Pulkrabek D.J., Dong Z., Venkatachalam M.A., Saikumar P. Bcl-2 prevents Bax oligomerization in the mitochondrial outer membrane. J. Biol. Chem. 276:2001;18361-18374.
34. Antonsson B., Montessuit S., Sanchez B., Martinou J.C. Bax is present as a high molecular weight oligomer/complex in the mitochondrial membrane of apoptotic cells. J. Biol. Chem. 276:2001;11615-11623.
35. Mikhailov V., Mikhailova M., Degenhardt K., Venkatachalam M.A., White E., Saikumar P. Association of Bax and Bak homo-oligomers in mitochondria. Bax requirement for Bak reorganization and cytochrome c release. J. Biol. Chem. 278:2003;5367-5376.
36. Nomura M., Shimizu S., Sugiyama T., Narita M., Ito T., Matsuda H., Tsujimoto Y. 14-3-3 Interacts directly with and negatively regulates pro-apoptotic Bax. J. Biol. Chem. 278:2003;2058-2065.
37. Yin X.M., Wang K., Gross A., Zhao Y., Zinkel S., Klocke B., Roth K.A., Korsmeyer S.J. Bid-deficient mice are resistant to Fas-induced hepatocellular apoptosis. Nature. 400:1999;886-891.
38. Sarig R., Zaltsman Y., Marcellus R.C., Flavell R., Mak T.W., Gross A. BID-D59A is a potent inducer of apoptosis in primary embryonic fibroblasts. J. Biol. Chem. 278:2003;10707-10715.
39. Madesh M., Antonsson B., Srinivasula S.M., Alnemri E.S., Hajnoczky G. Rapid kinetics of tBid-induced cytochrome c and Smac/DIABLO release and mitochondrial depolarization. J. Biol. Chem. 277:2002;5651-5659.
40. Li H., Zhu H., Xu C.J., Yuan J. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell. 94:1998;491-501.
41. Barry M., Heibein J.A., Pinkoski M.J., Lee S.F., Moyer R.W., Green D.R., Bleackley R.C. Granzyme B short-circuits the need for caspase 8 activity during granule-mediated cytotoxic T-lymphocyte killing by directly cleaving Bid. Mol. Cell. Biol. 20:2000;3781-3794.
42. Heibein J.A., Goping I.S., Barry M., Pinkoski M.J., Shore G.C., Green D.R., Bleackley R.C. Granzyme B-mediated cytochrome c release is regulated by the Bcl-2 family members bid and Bax. J. Exp. Med. 192:2000;1391-1402.
43. Alimonti J.B., Shi L., Baijal P.K., Greenberg A.H. Granzyme B induces BID-mediated cytochrome c release and mitochondrial permeability transition. J. Biol. Chem. 276:2001;6974-6982.
44. Reiners J.J. Jr., Caruso J.A., Mathieu P., Chelladurai B., Yin X.M., Kessel D. Release of cytochrome c and activation of pro-caspase-9 following lysosomal photodamage involves Bid cleavage. Cell Death Differ. 9:2002;934-944.
45. Stoka V., Turk B., Schendel S.L., Kim T.H., Cirman T., Snipas S.J., Ellerby L.M., Bredesen D., Freeze H., Abrahamson M., Bromme D., Krajewski S., Reed J.C., Yin X.M., Turk V., Salvesen G.S. Lysosomal protease pathways to apoptosis. Cleavage of bid, not pro-caspases, is the most likely route. J. Biol. Chem. 276:2001;3149-3157.
46. Mandic A., Viktorsson K., Strandberg L., Heiden T., Hansson J., Linder S., Shoshan M.C. Calpain-mediated Bid cleavage and calpain-independent Bak modulation: two separate pathways in cisplatin-induced apoptosis. Mol. Cell. Biol. 22:2002;3003-3013.
47. Chen M., He H., Zhan S., Krajewski S., Reed J.C., Gottlieb R.A. Bid is cleaved by calpain to an active fragment in vitro and during myocardial ischemia/reperfusion. J. Biol. Chem. 276:2001;30724-30728.
48. Korsmeyer S.J., Wei M.C., Saito M., Weiler S., Oh K.J., Schlesinger P.H. Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c. Cell Death Differ. 7:2000;1166-1173.
49. Wei M.C., Lindsten T., Mootha V.K., Weiler S., Gross A., Ashiya M., Thompson C.B., Korsmeyer S.J. tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c. Genes Dev. 14:2000;2060-2071.
50. Eskes R., Desagher S., Antonsson B., Martinou J.C. Bid induces the oligomerization and insertion of Bax into the outer mitochondrial membrane. Mol. Cell. Biol. 20:2000;929-935.
51. Grinberg M., Sarig R., Zaltsman Y., Frumkin D., Grammatikakis N., Reuveny E., Gross A. tBID homooligomerizes in the mitochondrial membrane to induce apoptosis. J. Biol. Chem. 277:2002;12237-12245.
52. Zamzami N., El Hamel C., Maisse C., Brenner C., Munoz-Pinedo C., Belzacq A.S., Costantini P., Vieira H., Loeffler M., Molle G., Kroemer G. Bid acts on the permeability transition pore complex to induce apoptosis. Oncogene. 19:2000;6342-6350.
53. Yi X., Yin X.M., Dong Z. Inhibition of Bid-induced apoptosis by Bcl-2: tBid insertion, Bax translocation and Bax/Bak oligomerization suppressed. J. Biol. Chem. 278:2003;16992-16999.
54. Finucane D.M., Bossy-Wetzel E., Waterhouse N.J., Cotter T.G., Green D.R. Bax-induced caspase activation and apoptosis via cytochrome c release from mitochondria is inhibitable by Bcl-xL. J. Biol. Chem. 274:1999;2225-2233.
55. Nakagawa T., Yuan J. Cross-talk between two cysteine protease families. Activation of caspase-12 by calpain in apoptosis. J. Cell Biol. 150:2000;887-894.
56. Clem R.J., Cheng E.H., Karp C.L., Kirsch D.G., Ueno K., Takahashi A., Kastan M.B., Griffin D.E., Earnshaw W.C., Veliuona M.A., Hardwick J.M. Modulation of cell death by Bcl-XL through caspase interaction. Proc. Natl. Acad. Sci. U. S. A. 95:1998;554-559.
57. Fujita N., Nagahashi A., Nagashima K., Rokudai S., Tsuruo T. Acceleration of apoptotic cell death after the cleavage of Bcl-XL protein by caspase-3-like proteases. Oncogene. 17:1998;1295-1304.
58. Basanez G., Zhang J., Chau B.N., Maksaev G.I., Frolov V.A., Brandt T.A., Burch J., Hardwick J.M., Zimmerberg J. Pro-apoptotic cleavage products of Bcl-xL form cytochrome c-conducting pores in pure lipid membranes. J. Biol. Chem. 276:2001;31083-31091.
59. Saito M., Korsmeyer S.J., Schlesinger P.H. BAX-dependent transport of cytochrome c reconstituted in pure liposomes. Nat. Cell Biol. 2:2000;553-555.
60. Kluck R.M., Esposti M.D., Perkins G., Renken C., Kuwana T., Bossy-Wetzel E., Goldberg M., Allen T., Barber M.J., Green D.R., Newmeyer D.D. The pro-apoptotic proteins, Bid and Bax, cause a limited permeabilization of the mitochondrial outer membrane that is enhanced by cytosol. J. Cell Biol. 147:1999;809-822.
61. Van Loo G., Demol H., van Gurp M., Hoorelbeke B., Schotte P., Beyaert R., Zhivotovsky B., Gevaert K., Declercq W., Vandekerckhove J., Vandenabeele P. A matrix-assisted laser desorption ionization post-source decay (MALDI-PSD) analysis of proteins released from isolated liver mitochondria treated with recombinant truncated Bid. Cell Death Differ. 9:2002;301-308.
62. Sutton V.R., Wowk M.E., Cancilla M., Trapani J.A. Caspase activation by granzyme B is indirect, and caspase autoprocessing requires the release of proapoptotic mitochondrial factors. Immunity. 18:2003;319-329.
63. Shimizu S., Narita M., Tsujimoto Y. Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Nature. 399:1999;483-487.
64. Shimizu S., Konishi A., Kodama T., Tsujimoto Y. BH4 domain of antiapoptotic Bcl-2 family members closes voltage-dependent anion channel and inhibits apoptotic mitochondrial changes and cell death. Proc. Natl. Acad. Sci. U. S. A. 97:2000;3100-3105.
65. Marzo I., Brenner C., Zamzami N., Jurgensmeier J.M., Susin S.A., Vieira H.L., Prevost M.C., Xie Z., Matsuyama S., Reed J.C., Kroemer G. Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis. Science. 281:1998;2027-2031.
66. Brenner C., Cadiou H., Vieira H.L., Zamzami N., Marzo I., Xie Z., Leber B., Andrews D., Duclohier H., Reed J.C., Kroemer G. Bcl-2 and Bax regulate the channel activity of the mitochondrial adenine nucleotide translocator. Oncogene. 19:2000;329-336.
67. Sugiyama T., Shimizu S., Matsuoka Y., Yoneda Y., Tsujimoto Y. Activation of mitochondrial voltage-dependent anion channel by a pro-apoptotic BH3-only protein Bim. Oncogene. 21:2002;4944-4956.
68. Shimizu S., Tsujimoto Y. Proapoptotic BH3-only Bcl-2 family members induce cytochrome c release, but not mitochondrial membrane potential loss, and do not directly modulate voltage-dependent anion channel activity. Proc. Natl. Acad. Sci. U. S. A. 97:2000;577-582.
69. Ferri K.F., Jacotot E., Blanco J., Este J.A., Zamzami N., Susin S.A., Xie Z., Brothers G., Reed J.C., Penninger J.M., Kroemer G. Apoptosis control in syncytia induced by the HIV type 1-envelope glycoprotein complex: role of mitochondria and caspases. J. Exp. Med. 192:2000;1081-1092.
70. Narita M., Shimizu S., Ito T., Chittenden T., Lutz R.J., Matsuda H., Tsujimoto Y. Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria. Proc. Natl. Acad. Sci. U. S. A. 95:1998;14681-14686.
71. Pastorino J.G., Chen S.T., Tafani M., Snyder J.W., Farber J.L. The overexpression of Bax produces cell death upon induction of the mitochondrial permeability transition. J. Biol. Chem. 273:1998;7770-7775.
72. Shimizu S., Matsuoka Y., Shinohara Y., Yoneda Y., Tsujimoto Y. Essential role of voltage-dependent anion channel in various forms of apoptosis in mammalian cells. J. Cell Biol. 152:2001;237-250.
73. Patterson S.D., Spahr C.S., Daugas E., Susin S.A., Irinopoulou T., Koehler C., Kroemer G. Mass spectrometric identification of proteins released from mitochondria undergoing permeability transition. Cell Death Differ. 7:2000;137-144.
74. Chang L.K., Johnson E.M. Jr. Cyclosporin A inhibits caspase-independent death of NGF-deprived sympathetic neurons: a potential role for mitochondrial permeability transition. J. Cell Biol. 157:2002;771-781.
75. Shimizu S., Ide T., Yanagida T., Tsujimoto Y. Electrophysiological study of a novel large pore formed by Bax and the voltage-dependent anion channel that is permeable to cytochrome c. J. Biol. Chem. 275:2000;12321-12325.
76. Du C., Fang M., Li Y., Li L., Wang X. Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell. 102:2000;33-42.
77. Srinivasula S.M., Hegde R., Saleh A., Datta P., Shiozaki E., Chai J., Lee R.A., Robbins P.D., Fernandes-Alnemri T., Shi Y., Alnemri E.S. A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis. Nature. 410:2001;112-116.
78. Verhagen A.M., Ekert P.G., Pakusch M., Silke J., Connolly L.M., Reid G.E., Moritz R.L., Simpson R.J., Vaux D.L. Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell. 102:2000;43-53.
79. Kluck R.M., Bossy-Wetzel E., Green D.R., Newmeyer D.D. The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science. 275:1997;1132-1136.
80. van Loo G., van Gurp M., Depuydt B., Srinivasula S.M., Rodriguez I., Alnemri E.S., Gevaert K., Vandekerckhove J., Declercq W., Vandenabeele P. The serine protease Omi/HtrA2 is released from mitochondria during apoptosis. Omi interacts with caspase-inhibitor XIAP and induces enhanced caspase activity. Cell Death Differ. 9:2002;20-26.
81. Susin S.A., Lorenzo H.K., Zamzami N., Marzo I., Snow B.E., Brothers G.M., Mangion J., Jacotot E., Costantini P., Loeffler M., Larochette N., Goodlett D.R., Aebersold R., Siderovski D.P., Penninger J.M., Kroemer G. Molecular characterization of mitochondrial apoptosis-inducing factor. Nature. 397:1999;441-446.
82. van Loo G., Schotte P., van Gurp M., Demol H., Hoorelbeke B., Gevaert K., Rodriguez I., Ruiz-Carrillo A., Vandekerckhove J., Declercq W., Beyaert R., Vandenabeele P. Endonuclease G: a mitochondrial protein released in apoptosis and involved in caspase-independent DNA degradation. Cell Death Differ. 8:2001;1136-1142.
83. Verhagen A.M., Silke J., Ekert P.G., Pakusch M., Kaufmann H., Connolly L.M., Day C.L., Tikoo A., Burke R., Wrobel C., Moritz R.L., Simpson R.J., Vaux D.L. HtrA2 promotes cell death through its serine protease activity and its ability to antagonize inhibitor of apoptosis proteins. J. Biol. Chem. 277:2002;445-454.
84. Daugas E., Nochy D., Ravagnan L., Loeffler M., Susin S.A., Zamzami N., Kroemer G. Apoptosis-inducing factor (AIF): a ubiquitous mitochondrial oxidoreductase involved in apoptosis. FEBS Lett. 476:2000;118-123.
85. Arnoult D., Parone P., Martinou J.C., Antonsson B., Estaquier J., Ameisen J.C. Mitochondrial release of apoptosis-inducing factor occurs downstream of cytochrome c release in response to several proapoptotic stimuli. J. Cell Biol. 159:2002;923-929.
86. Adrain C., Creagh E.M., Martin S.J. Apoptosis-associated release of Smac/DIABLO from mitochondria requires active caspases and is blocked by Bcl-2. EMBO J. 20:2001;6627-6636.
87. Springs S.L., Diavolitsis V.M., Goodhouse J., McLendon G.L. The kinetics of translocation of Smac/DIABLO from the mitochondria to the cytosol in HeLa cells. J. Biol. Chem. 277:2002;45715-45718.
88. Hegde R., Srinivasula S.M., Zhang Z., Wassell R., Mukattash R., Cilenti L., DuBois G., Lazebnik Y., Zervos A.S., Fernandes-Alnemri T., Alnemri E.S. Identification of Omi/HtrA2 as a mitochondrial apoptotic serine protease that disrupts inhibitor of apoptosis protein-caspase interaction. J. Biol. Chem. 277:2002;432-438.
89. Li L.Y., Luo X., Wang X. Endonuclease G is an apoptotic DNase when released from mitochondria. Nature. 412:2001;95-99.
90. Klein J.A., Longo-Guess C.M., Rossmann M.P., Seburn K.L., Hurd R.E., Frankel W.N., Bronson R.T., Ackerman S.L. The harlequin mouse mutation downregulates apoptosis-inducing factor. Nature. 419:2002;367-374.
91. Loeffler M., Daugas E., Susin S.A., Zamzami N., Metivier D., Nieminen A.L., Brothers G., Penninger J.M., Kroemer G. Dominant cell death induction by extramitochondrially targeted apoptosis-inducing factor. FASEB J. 15:2001;758-767.
92. Susin S.A., Daugas E., Ravagnan L., Samejima K., Zamzami N., Loeffler M., Costantini P., Ferri K.F., Irinopoulou T., Prevost M.C., Brothers G., Mak T.W., Penninger J., Earnshaw W.C., Kroemer G. Two distinct pathways leading to nuclear apoptosis. J. Exp. Med. 192:2000;571-580.
93. Fonfria E., Dare E., Benelli M., Sunol C., Ceccatelli S. Translocation of apoptosis-inducing factor in cerebellar granule cells exposed to neurotoxic agents inducing oxidative stress. Eur. J. Neurosci. 16:2002;2013-2016.
94. Braun J.S., Sublett J.E., Freyer D., Mitchell T.J., Cleveland J.L., Tuomanen E.I., Weber J.R. Pneumococcal pneumolysin and H(2)O(2) mediate brain cell apoptosis during meningitis. J. Clin. Invest. 109:2002;19-27.
95. Marzo I., Perez-Galan P., Giraldo P., Rubio-Felix D., Anel A., Naval J. Cladribine induces apoptosis in human leukaemia cells by caspase-dependent and-independent pathways acting on mitochondria. Biochem. J. 359:2001;537-546.
96. Pardo J., Perez-Galan P., Gamen S., Marzo I., Monleon I., Kaspar A.A., Susin S.A., Kroemer G., Krensky A.M., Naval J., Anel A. A role of the mitochondrial apoptosis-inducing factor in granulysin-induced apoptosis. J. Immunol. 167:2001;1222-1229.
97. Zhang X., Chen J., Graham S.H., Du L., Kochanek P.M., Draviam R., Guo F., Nathaniel P.D., Szabo C., Watkins S.C., Clark R.S. Intranuclear localization of apoptosis-inducing factor (AIF) and large scale DNA fragmentation after traumatic brain injury in rats and in neuronal cultures exposed to peroxynitrite. J. Neurochem. 82:2002;181-191.
98. Cregan S.P., Fortin A., MacLaurin J.G., Callaghan S.M., Cecconi F., Yu S.W., Dawson T.M., Dawson V.L., Park D.S., Kroemer G., Slack R.S. Apoptosis-inducing factor is involved in the regulation of caspase-independent neuronal cell death. J. Cell Biol. 158:2002;507-517.
99. Murahashi H., Azuma H., Zamzami N., Furuya K.J., Ikebuchi K., Yamaguchi M., Yamada Y., Sato N., Fujihara M., Kroemer G., Ikeda H. Possible contribution of apoptosis-inducing factor (AIF) and reactive oxygen species (ROS) to UVB-induced caspase-independent cell death in the T cell line Jurkat. J. Leukoc. Biol. 73:2003;399-406.
100. Liptay S., Fulda S., Schanbacher M., Bourteele S., Ferri K.F., Kroemer G., Adler G., Debatin K.M., Schmid R.M. Molecular mechanisms of sulfasalazine-induced T-cell apoptosis. Br. J. Pharmacol. 137:2002;608-620.
101. Yu S.W., Wang H., Poitras M.F., Coombs C., Bowers W.J., Federoff H.J., Poirier G.G., Dawson T.M., Dawson V.L. Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor. Science. 297:2002;259-263.
102. Arnoult D., Tatischeff I., Estaquier J., Girard M., Sureau F., Tissier J.P., Grodet A., Dellinger M., Traincard F., Kahn A., Ameisen J.C., Petit P.X. On the evolutionary conservation of the cell death pathway: mitochondrial release of an apoptosis-inducing factor during Dictyostelium discoideum cell death. Mol. Biol. Cell. 12:2001;3016-3030.
103. Joza N., Susin S.A., Daugas E., Stanford W.L., Cho S.K., Li C.Y., Sasaki T., Elia A.J., Cheng H.Y., Ravagnan L., Ferri K.F., Zamzami N., Wakeham A., Hakem R., Yoshida H., Kong Y.Y., Mak T.W., Zuniga-Pflucker J.C., Kroemer G., Penninger J.M. Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death. Nature. 410:2001;549-554.
104. Wang X., Yang C., Chai J., Shi Y., Xue D. Mechanisms of AIF-mediated apoptotic DNA degradation in Caenorhabditis elegans. Science. 298:2002;1587-1592.
105. Hisatomi T., Sakamoto T., Murata T., Yamanaka I., Oshima Y., Hata Y., Ishibashi T., Inomata H., Susin S.A., Kroemer G. Relocalization of apoptosis-inducing factor in photoreceptor apoptosis induced by retinal detachment in vivo. Am. J. Pathol. 158:2001;1271-1278.
106. Chen J., Flannery J.G., LaVail M.M., Steinberg R.H., Xu J., Simon M.I. bcl-2 overexpression reduces apoptotic photoreceptor cell death in three different retinal degenerations. Proc. Natl. Acad. Sci. U. S. A. 93:1996;7042-7047.
107. Ravagnan L., Gurbuxani S., Susin S.A., Maisse C., Daugas E., Zamzami N., Mak T., Jaattela M., Penninger J.M., Garrido C., Kroemer G. Heat-shock protein 70 antagonizes apoptosis-inducing factor. Nat. Cell Biol. 3:2001;839-843.
108. Joseph B., Marchetti P., Formstecher P., Kroemer G., Lewensohn R., Zhivotovsky B. Mitochondrial dysfunction is an essential step for killing of non-small cell lung carcinomas resistant to conventional treatment. Oncogene. 21:2002;65-77.
109. Ye H., Cande C., Stephanou N.C., Jiang S., Gurbuxani S., Larochette N., Daugas E., Garrido C., Kroemer G., Wu H. DNA binding is required for the apoptogenic action of apoptosis inducing factor. Nat. Struct. Biol. 9:2002;680-684.
110. Basu A., Johnson D.E., Woolard M.D. Potentiation of tumor necrosis factor-alpha-induced cell death by rottlerin through a cytochrome-C-independent pathway. Exp. Cell Res. 278:2002;209-214.
111. Fulda S., Meyer E., Debatin K.M. Inhibition of TRAIL-induced apoptosis by Bcl-2 overexpression. Oncogene. 21:2002;2283-2294.
112. Singh R., Upadhyay G., Godbole M.M. Hypothyroidism alters mitochondrial morphology and induces release of apoptogenic proteins during rat cerebellar development. J. Endocrinol. 176:2003;321-329.
113. van Loo G., Saelens X., Matthijssens F., Schotte P., Beyaert R., Declercq W., Vandenabeele P. Caspases are not localized in mitochondria during life or death. Cell Death Differ. 9:2002;1207-1211.
114. Enari M., Sakahira H., Yokoyama H., Okawa K., Iwamatsu A., Nagata S. A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature. 391:1998;43-50.
115. Sakahira H., Enari M., Nagata S. Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis. Nature. 391:1998;96-99.
116. Janicke R.U., Ng P., Sprengart M.L., Porter A.G. Caspase-3 is required for alpha-fodrin cleavage but dispensable for cleavage of other death substrates in apoptosis. J. Biol. Chem. 273:1998;15540-15545.
117. Thomas D.A., Du C., Xu M., Wang X., Ley T.J. DFF45/ICAD can be directly processed by granzyme B during the induction of apoptosis. Immunity. 12:2000;621-632.
118. Sharif-Askari E., Alam A., Rheaume E., Beresford P.J., Scotto C., Sharma K., Lee D., DeWolf W.E., Nuttall M.E., Lieberman J., Sekaly R.P. Direct cleavage of the human DNA fragmentation factor-45 by granzyme B induces caspase-activated DNase release and DNA fragmentation. EMBO J. 20:2001;3101-3113.
119. Yakovlev A.G., Di X., Movsesyan V., Mullins P.G., Wang G., Boulares H., Zhang J., Xu M., Faden A.I. Presence of DNA fragmentation and lack of neuroprotective effect in DFF45 knockout mice subjected to traumatic brain injury. Mol. Med. 7:2001;205-216.
120. McIlroy D., Tanaka M., Sakahira H., Fukuyama H., Suzuki M., Yamamura K., Ohsawa Y., Uchiyama Y., Nagata S. An auxiliary mode of apoptotic DNA fragmentation provided by phagocytes. Genes Dev. 14:2000;549-558.
121. Cote J., Ruiz-Carrillo A. Primers for mitochondrial DNA replication generated by endonuclease G. Science. 261:1993;765-769.
122. Davies A.M., Hershman S., Stabley G.J., Hoek J.B., Peterson J., Cahill A. A Ca2+-induced mitochondrial permeability transition causes complete release of rat liver endonuclease G activity from its exclusive location within the mitochondrial intermembrane space. Identification of a novel endo-exonuclease activity residing within the mitochondrial matrix. Nucleic Acids Res. 31:2003;1364-1373.
123. Parrish J., Li L., Klotz K., Ledwich D., Wang X., Xue D. Mitochondrial endonuclease G is important for apoptosis in C. elegans. Nature. 412:2001;90-94.
124. Faccio L., Fusco C., Chen A., Martinotti S., Bonventre J.V., Zervos A.S. 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. 275:2000;2581-2588.
125. Spiess C., Beil A., Ehrmann M. A temperature-dependent switch from chaperone to protease in a widely conserved heat shock protein. Cell. 97:1999;339-347.
126. Martins L.M., Iaccarino I., Tenev T., Gschmeissner S., Totty N.F., Lemoine N.R., Savopoulos J., Gray C.W., Creasy C.L., Dingwall C., Downward J. The serine protease Omi/HtrA2 regulates apoptosis by binding XIAP through a reaper-like motif. J. Biol. Chem. 277:2002;439-444.
127. Yamaguchi H., Bhalla K., Wang H.G. Bax plays a pivotal role in thapsigargin-induced apoptosis of human colon cancer HCT116 cells by controlling Smac/Diablo and Omi/HtrA2 release from mitochondria. Cancer Res. 63:2003;1483-1489.
128. Suzuki Y., Imai Y., Nakayama H., Takahashi K., Takio K., Takahashi R. A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death. Mol. Cell. 8:2001;613-621.
129. Gray C.W., Ward R.V., Karran E., Turconi S., Rowles A., Viglienghi D., Southan C., Barton A., Fantom K.G., West A., Savopoulos J., Hassan N.J., Clinkenbeard H., Hanning C., Amegadzie B., Davis J.B., Dingwall C., Livi G.P., Creasy C.L. Characterization of human HtrA2, a novel serine protease involved in the mammalian cellular stress response. Eur. J. Biochem. 267:2000;5699-5710.
130. Cilenti L., Lee Y., Hess S., Srinivasula S., Park K.M., Junqueira D., Davis H., Bonventre J.V., Alnemri E.S., Zervos A.S. Characterization of a novel and specific inhibitor for the pro-apoptotic protease Omi/HtrA2. J. Biol. Chem. 278:2003;11489-11494.
131. Lacana E., Ganjei J.K., Vito P., D'Adamio L. Dissociation of apoptosis and activation of IL-1beta-converting enzyme/Ced-3 proteases by ALG-2 and the truncated Alzheimer's gene ALG-3. J. Immunol. 158:1997;5129-5135.
132. Wright S.C., Schellenberger U., Wang H., Kinder D.H., Talhouk J.W., Larrick J.W. Activation of CPP32-like proteases is not sufficient to trigger apoptosis: inhibition of apoptosis by agents that suppress activation of AP24, but not CPP32-like activity. J. Exp. Med. 186:1997;1107-1117.
133. Maianski N.A., Roos D., Kuijpers T.W. Tumor necrosis factor alpha induces a caspase-independent death pathway in human neutrophils. Blood. 101:2003;1987-1995.
134. Mathiasen I.S., Lademann U., Jaattela M. Apoptosis induced by vitamin D compounds in breast cancer cells is inhibited by Bcl-2 but does not involve known caspases or p53. Cancer Res. 59:1999;4848-4856.
135. Nylandsted J., Rohde M., Brand K., Bastholm L., Elling F., Jaattela M. Selective depletion of heat shock protein 70 (Hsp70) activates a tumor-specific death program that is independent of caspases and bypasses Bcl-2. Proc. Natl. Acad. Sci. U. S. A. 97:2000;7871-7876.
136. Petit F., Arnoult D., Lelievre J.D., Moutouh-de Parseval L., Hance A.J., Schneider P., Corbeil J., Ameisen J.C., Estaquier J. Productive HIV-1 infection of primary CD4+ T cells induces mitochondrial membrane permeabilization leading to a caspase-independent cell death. J. Biol. Chem. 277:2002;1477-1487.
137. Bao J.J., Le X.F., Wang R.Y., Yuan J., Wang L., Atkinson E.N., LaPushin R., Andreeff M., Fang B., Yu Y., Bast R.C. Jr. Reexpression of the tumor suppressor gene ARHI induces apoptosis in ovarian and breast cancer cells through a caspase-independent calpain-dependent pathway. Cancer Res. 62:2002;7264-7272.
138. Lindenboim L., Yuan J., Stein R. Bcl-xS and Bax induce different apoptotic pathways in PC12 cells. Oncogene. 19:2000;1783-1793.
139. Chi S., Kitanaka C., Noguchi K., Mochizuki T., Nagashima Y., Shirouzu M., Fujita H., Yoshida M., Chen W., Asai A., Himeno M., Yokoyama S., Kuchino Y. Oncogenic Ras triggers cell suicide through the activation of a caspase-independent cell death program in human cancer cells. Oncogene. 18:1999;2281-2290.
140. Belmokhtar C.A., Hillion J., Segal-Bendirdjian E. Staurosporine induces apoptosis through both caspase-dependent and caspase-independent mechanisms. Oncogene. 20:2001;3354-3362.
141. Kim K.D., Choe Y.K., Choe I.S., Lim J.S. Inhibition of glucocorticoid-mediated, caspase-independent dendritic cell death by CD40 activation. J. Leukoc. Biol. 69:2001;426-434.
142. Fujimaki S., Kubohara Y., Kobayashi I., Kojima I. Caspase-independent apoptosis induced by differentiation-inducing factor of Dicytostelium discoideum in INS-1 cells. Eur. J. Pharmacol. 421:2001;93-100.
143. Uzzo R.G., Dulin N., Bloom T., Bukowski R., Finke J.H., Kolenko V. Inhibition of NFkappaB induces caspase-independent cell death in human T lymphocytes. Biochem. Biophys. Res. Commun. 287:2001;895-899.
144. Zhu D.M., Uckun F.M. Cathepsin inhibition induces apoptotic death in human leukemia and lymphoma cells. Leuk. Lymphoma. 39:2000;343-354.
145. Berndt C., Mopps B., Angermuller S., Gierschik P., Krammer P.H. CXCR4 and CD4 mediate a rapid CD95-independent cell death in CD4(+) T cells. Proc. Natl. Acad. Sci. U. S. A. 95:1998;12556-12561.
146. Deas O., Dumont C., MacFarlane M., Rouleau M., Hebib C., Harper F., Hirsch F., Charpentier B., Cohen G.M., Senik A. Caspase-independent cell death induced by anti-CD2 or staurosporine in activated human peripheral T lymphocytes. J. Immunol. 161:1998;3375-3383.
147. Lesage S., Steff A.M., Philippoussis F., Page M., Trop S., Mateo V., Hugo P. CD4+CD8+ thymocytes are preferentially induced to die following CD45 cross-linking, through a novel apoptotic pathway. J. Immunol. 159:1997;4762-4771.
148. Sohn H.W., Choi E.Y., Kim S.H., Lee I.S., Chung D.H., Sung U.A., Hwang D.H., Cho S.S., Jun B.H., Jang J.J., Chi J.G., Park S.H. Engagement of CD99 induces apoptosis through a calcineurin-independent pathway in Ewing's sarcoma cells. Am. J. Pathol. 153:1998;1937-1945.
149. Carmody R.J., Cotter T.G. Oxidative stress induces caspase-independent retinal apoptosis in vitro. Cell Death Differ. 7:2000;282-291.
150. Ren J.G., Xia H.L., Just T., Dai Y.R. Hydroxyl radical-induced apoptosis in human tumor cells is associated with telomere shortening but not telomerase
151. Okuno S., Shimizu S., Ito T., Nomura M., Hamada E., Tsujimoto Y., Matsuda H. Bcl-2 prevents caspase-independent cell death. J. Biol. Chem. 273:1998;34272-34277.
152. Doerfler P., Forbush K.A., Perlmutter R.M. Caspase enzyme activity is not essential for apoptosis during thymocyte development. J. Immunol. 164:2000;4071-4079.