Cancer Chemotherapy and Pharmacology

, Volume 57, Issue 5, pp 545–553

Role of mitochondria as the gardens of cell death

Review

Abstract

Mitochondria play a crucial role in regulating cell death, which is mediated by outer membrane permeabilization in response to death triggers such as DNA damage and growth factor deprivation. Mitochondrial membrane permeabilization induces the release of cytochrome c, Smac/DIABLO, and AIF, which are regulated by proapoptotic and antiapoptotic proteins such as Bax/Bak and Bcl-2/xL in caspase-dependent and caspase-independent apoptosis pathways. Mitochondrial dysfunction is mediated in two ways. The first is by increased calcium in mitochondria derived from endoplasmic reticulum (ER); this calcium increase is regulated by Bcl-2 and Bax through the ER-mitochondria connection and the unfolded protein response in the ER. The second is by the lysosomal enzyme cathepsin, which activates Bid through lysosome–mitochondria cross-signaling. The genomic responses in intracellular organelles after DNA damage are controlled and amplified in the cross-signaling via mitochondria; such signals induce apoptosis, autophagy, and other cell death pathways. This review discusses the recent advancements in understanding the molecular mechanism of mitochondria-mediated cell death.

Keywords

Mitochondria Apoptosis Autophagy Endoplasmic reticulum Lysosome 

Abbreviations

Smac

Second mitochondria-derived activator of caspase

DIABLO

Direct inhibitor of apoptosis-binding protein with low pI

AIF

Apoptosis-inducing factor

MMP

Mitochondrial membrane permeabilization

VDAC

Voltage-dependent anion channel

ANT

Adenine nucleotide translocator

ROS

Reactive oxygen species

ER

Endoplasmic reticulum

PCD

Programmed cell death

SERCA

Sarcoplasmic/ER Ca2+ ATPase

UPR

Unfolded protein response

References

  1. 1.
    Acehan D, Jiang X, Morgan DG, Heuser JE, Wang X, Akey CW (2002) Three-dimensional structure of the apoptosome: implications for assembly, procaspase-9 binding, and activation. Mol Cell 9:423CrossRefPubMedGoogle Scholar
  2. 2.
    Akay C, Thomas C III, Gazitt Y (2004) Arsenic trioxide and paclitaxel induce apoptosis by different mechanisms. Cell Cycle 3:324PubMedGoogle Scholar
  3. 3.
    Baliga B, Kumar S (2003) Apaf-1/cytochrome c apoptosome: an essential initiator of caspase activation or just a sideshow? Cell Death Differ 10:16CrossRefPubMedGoogle Scholar
  4. 4.
    Baptiste N, Prives C (2004) p53 in the cytoplasm: a question of overkill? Cell 116:487CrossRefPubMedGoogle Scholar
  5. 5.
    Bidere N, Lorenzo HK, Carmona S, Laforge M, Harper F, Dumont C, Senik A (2003) Cathepsin D triggers Bax activation, resulting in selective apoptosis-inducing factor (AIF) relocation in T lymphocytes entering the early commitment phase to apoptosis. J Biol Chem 278:31401PubMedGoogle Scholar
  6. 6.
    Boise LH, Gonzalez-Garcia M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Nunez G, Thompson CB (1993) bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell 74:597CrossRefPubMedGoogle Scholar
  7. 7.
    Bouillet P, Strasser A (2002) BH3-only proteins—evolutionarily conserved proapoptotic Bcl-2 family members essential for initiating programmed cell death. J Cell Sci 115:1567PubMedGoogle Scholar
  8. 8.
    Boulares AH, Zoltoski AJ, Contreras FJ, Yakovlev AG, Yoshihara K, Smulson ME (2002) Regulation of DNAS1L3 endonuclease activity by poly(ADP-ribosyl)ation during etoposide-induced apoptosis. Role of poly(ADP-ribose) polymerase-1 cleavage in endonuclease activation. J Biol Chem 277:372CrossRefPubMedGoogle Scholar
  9. 9.
    Boya P, Gonzalez-Polo RA, Poncet D, Andreau K, Vieira HL, Roumier T, Perfettini JL, Kroemer G (2003) Mitochondrial membrane permeabilization is a critical step of lysosome-initiated apoptosis induced by hydroxychloroquine. Oncogene 22:3927CrossRefPubMedGoogle Scholar
  10. 10.
    Breckenridge DG, Germain M, Mathai JP, Nguyen M, Shore GC (2003) Regulation of apoptosis by endoplasmic reticulum pathways. Oncogene 22:8608CrossRefPubMedGoogle Scholar
  11. 11.
    Bursch W (2001) The autophagosomal-lysosomal compartment in programmed cell death. Cell Death Differ 8:569CrossRefPubMedGoogle Scholar
  12. 12.
    Bursch W, Ellinger A, Gerner C, Frohwein U, Schulte-Hermann R (2000) Programmed cell death (PCD). Apoptosis, autophagic PCD, or others? Ann N Y Acad Sci 926:1PubMedCrossRefGoogle Scholar
  13. 13.
    Chami M, Prandini A, Campanella M, Pinton P, Szabadkai G, Reed JC, Rizzuto R (2004) Bcl-2 and Bax exert opposing effects on Ca2+ signaling, which do not depend on their putative pore-forming region. J Biol Chem 279:54581CrossRefPubMedGoogle Scholar
  14. 14.
    Chipuk JE, Green DR (2003) p53’s believe it or not: lessons on transcription-independent death. J Clin Immunol 23:355CrossRefPubMedGoogle Scholar
  15. 15.
    Chipuk JE, Green DR (2004) Cytoplasmic p53: bax and forward. Cell Cycle 3:429PubMedGoogle Scholar
  16. 16.
    Chipuk JE, Kuwana T, Bouchier-Hayes L, Droin NM, Newmeyer DD, Schuler M, Green DR (2004) Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science 303:1010CrossRefPubMedGoogle Scholar
  17. 17.
    Chittenden T (2002) BH3 domains: intracellular death-ligands critical for initiating apoptosis. Cancer Cell 2:165CrossRefPubMedGoogle Scholar
  18. 18.
    Chittenden T, Harrington EA, O’Connor R, Flemington C, Lutz RJ, Evan GI, Guild BC (1995) Induction of apoptosis by the Bcl-2 homologue Bak. Nature 374:733CrossRefPubMedGoogle Scholar
  19. 19.
    Chuang PI, Yee E, Karsan A, Winn RK, Harlan JM (1998) A1 is a constitutive and inducible Bcl-2 homologue in mature human neutrophils. Biochem Biophys Res Commun 249:361CrossRefPubMedGoogle Scholar
  20. 20.
    Cirman T, Oresic K, Mazovec GD, Turk V, Reed JC, Myers RM, Salvesen GS, Turk B (2004) Selective disruption of lysosomes in HeLa cells triggers apoptosis mediated by cleavage of Bid by multiple papain-like lysosomal cathepsins. J Biol Chem 279:3578CrossRefPubMedGoogle Scholar
  21. 21.
    Cregan SP, Dawson VL, Slack RS (2004) Role of AIF in caspase-dependent and caspase-independent cell death. Oncogene 23:2785CrossRefPubMedGoogle Scholar
  22. 22.
    De Giorgi F, Lartigue L, Bauer MK, Schubert A, Grimm S, Hanson GT, Remington SJ, Youle RJ, Ichas F (2002) The permeability transition pore signals apoptosis by directing Bax translocation and multimerization. FASEB J 16:607PubMedGoogle Scholar
  23. 23.
    Demaurex N, Distelhorst C (2003) Cell biology. Apoptosis—the calcium connection. Science 300:65CrossRefPubMedGoogle Scholar
  24. 24.
    Donovan M, Cotter TG (2004) Control of mitochondrial integrity by Bcl-2 family members and caspase-independent cell death. Biochim Biophys Acta 1644:133CrossRefPubMedGoogle Scholar
  25. 25.
    Du C, Fang M, Li Y, Li L, Wang X (2000) Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 102:33CrossRefPubMedGoogle Scholar
  26. 26.
    Erster S, Mihara M, Kim RH, Petrenko O, Moll UM (2004) In vivo mitochondrial p53 translocation triggers a rapid first wave of cell death in response to DNA damage that can precede p53 target gene activation. Mol Cell Biol 24:6728CrossRefPubMedGoogle Scholar
  27. 27.
    Fehrenbacher N, Gyrd-Hansen M, Poulsen B, Felbor U, Kallunki T, Boes M, Weber E, Leist M, Jaattela M (2004) Sensitization to the lysosomal cell death pathway upon immortalization and transformation. Cancer Res 64:5301CrossRefPubMedGoogle Scholar
  28. 28.
    Fernandez PM, Tabbara SO, Jacobs LK, Manning FC, Tsangaris TN, Schwartz AM, Kennedy KA, Patierno SR (2000) Overexpression of the glucose-regulated stress gene GRP78 in malignant but not benign human breast lesions. Breast Cancer Res Treat 59:15CrossRefPubMedGoogle Scholar
  29. 29.
    Fribley A, Zeng Q, Wang CY. (2004) Proteasome inhibitor PS-341 induces apoptosis through induction of endoplasmic reticulum stress-reactive oxygen species in head and neck squamous cell carcinoma cells. Mol Cell Biol 24:9695CrossRefPubMedGoogle Scholar
  30. 30.
    Fridman JS, Lowe SW (2003) Control of apoptosis by p53. Oncogene 22:9030CrossRefPubMedGoogle Scholar
  31. 31.
    Gajkowska B, Wojewodzka U, Gajda J (2004) Translocation of Bax and Bid to mitochondria, endoplasmic reticulum and nuclear envelope: possible control points in apoptosis. J Mol Histol 35:11CrossRefPubMedGoogle Scholar
  32. 32.
    Gibson L, Holmgreen SP, Huang DC, Bernard O, Copeland NG, Jenkins NA, Sutherland GR, Baker E, Adams JM, Cory S (1996) bcl-w, a novel member of the bcl-2 family, promotes cell survival. Oncogene 13:665PubMedGoogle Scholar
  33. 33.
    Goonesinghe A, Mundy ES, Smith M, Khosravi-Far R, Martinou JC, Degli Esposti M (2004) Pro-apoptotic Bid induces membrane perturbation by inserting selected lysolipids into the bilayer. Biochem J 387:109Google Scholar
  34. 34.
    Gosky D, Chatterjee S (2003) Down-regulation of topoisomerase II alpha is caused by up-regulation of GRP78. Biochem Biophys Res Commun 300:327CrossRefPubMedGoogle Scholar
  35. 35.
    Gozuacik D, Kimchi A (2004) Autophagy as a cell death and tumor suppressor mechanism. Oncogene 23:2891CrossRefPubMedGoogle Scholar
  36. 36.
    Green DR, Kroemer G (2004) The pathophysiology of mitochondrial cell death. Science 305:626CrossRefPubMedGoogle Scholar
  37. 37.
    Griffiths GJ, Dubrez L, Morgan CP, Jones NA, Whitehouse J, Corfe BM, Dive C, Hickman JA (1999) Cell damage-induced conformational changes of the pro-apoptotic protein Bak in vivo precede the onset of apoptosis. J Cell Biol 144:903CrossRefPubMedGoogle Scholar
  38. 38.
    Gurova KV, Gudkov AV (2003) Paradoxical role of apoptosis in tumor progression. J Cell Biochem 88:128CrossRefPubMedGoogle Scholar
  39. 39.
    Hampton RY (2000) ER stress response: getting the UPR hand on misfolded proteins. Curr Biol 10:R518CrossRefPubMedGoogle Scholar
  40. 40.
    He H, Lam M, McCormick TS, Distelhorst CW (1997) Maintenance of calcium homeostasis in the endoplasmic reticulum by Bcl-2. J Cell Biol 138:1219CrossRefPubMedGoogle Scholar
  41. 41.
    He L, Lemasters JJ (2002) Regulated and unregulated mitochondrial permeability transition pores: a new paradigm of pore structure and function? FEBS Lett 512:1CrossRefPubMedGoogle Scholar
  42. 42.
    Hegde R, Srinivasula SM, Zhang Z, Wassell R, Mukattash R, Cilenti L, DuBois G, Lazebnik Y, Zervos AS, Fernandes-Alnemri T, Alnemri ES (2002) Identification of Omi/HtrA2 as a mitochondrial apoptotic serine protease that disrupts inhibitor of apoptosis protein-caspase interaction. J Biol Chem 277:432CrossRefPubMedGoogle Scholar
  43. 43.
    Huang XJ, Wiernik PH, Klein RS, Gallagher RE (1999) Arsenic trioxide induces apoptosis of myeloid leukemia cells by activation of caspases. Med Oncol 16:58PubMedGoogle Scholar
  44. 44.
    Isahara K, Ohsawa Y, Kanamori S, Shibata M, Waguri S, Sato N, Gotow T, Watanabe T, Momoi T, Urase K, Kominami E, Uchiyama Y (1999) Regulation of a novel pathway for cell death by lysosomal aspartic and cysteine proteinases. Neuroscience 91:233CrossRefPubMedGoogle Scholar
  45. 45.
    Ishitsuka K, Hanada S, Uozumi K, Utsunomiya A, Arima T (2000) Arsenic trioxide and the growth of human T-cell leukemia virus type I infected T-cell lines. Leuk Lymphoma 37:649PubMedGoogle Scholar
  46. 46.
    Iwama K, Nakajo S, Aiuchi T, Nakaya K (2001) Apoptosis induced by arsenic trioxide in leukemia U937 cells is dependent on activation of p38, inactivation of ERK and the Ca2+-dependent production of superoxide. Int J Cancer 92:518CrossRefPubMedGoogle Scholar
  47. 47.
    Jacotot E, Costantini P, Laboureau E, Zamzami N, Susin SA, Kroemer G (1999) Mitochondrial membrane permeabilization during the apoptotic process. Ann N Y Acad Sci 887:18PubMedCrossRefGoogle Scholar
  48. 48.
    Jiang M, Milner J (2003) Bcl-2 constitutively suppresses p53-dependent apoptosis in colorectal cancer cells. Genes Dev 17:832CrossRefPubMedGoogle Scholar
  49. 49.
    Johansson AC, Steen H, Ollinger K, Roberg K (2003) Cathepsin D mediates cytochrome c release and caspase activation in human fibroblast apoptosis induced by staurosporine. Cell Death Differ 10:1253CrossRefPubMedGoogle Scholar
  50. 50.
    Kanzawa T, Kondo Y, Ito H, Kondo S, Germano I (2003) Induction of autophagic cell death in malignant glioma cells by arsenic trioxide. Cancer Res 63:2103PubMedGoogle Scholar
  51. 51.
    Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239PubMedGoogle Scholar
  52. 52.
    Kim R (2005) Recent advances in understanding the cell death pathways activated by anticancer therapy. Cancer 103:1551CrossRefPubMedGoogle Scholar
  53. 53.
    Korsmeyer SJ, Wei MC, Saito M, Weiler S, Oh KJ, Schlesinger PH (2000) Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c. Cell Death Differ 7:1166CrossRefPubMedGoogle Scholar
  54. 54.
    Kozopas KM, Yang T, Buchan HL, Zhou P, Craig RW (1993) MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2. Proc Natl Acad Sci USA 90:3516PubMedGoogle Scholar
  55. 55.
    Lemasters JJ, Qian T, He L, Kim JS, Elmore SP, Cascio WE, Brenner DA (2002) Role of mitochondrial inner membrane permeabilization in necrotic cell death, apoptosis, and autophagy. Antioxid Redox Signal 4:769CrossRefPubMedGoogle Scholar
  56. 56.
    Letai A, Bassik MC, Walensky LD, Sorcinelli MD, Weiler S, Korsmeyer SJ (2002) Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell 2:183CrossRefPubMedGoogle Scholar
  57. 57.
    Li H, Zhu H, Xu CJ, Yuan J (1998) Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94:491CrossRefPubMedGoogle Scholar
  58. 58.
    Li LY, Luo X, Wang X (2001) Endonuclease G is an apoptotic DNase when released from mitochondria. Nature 412:95CrossRefPubMedGoogle Scholar
  59. 59.
    Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, Levine B (1999) Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402:672CrossRefPubMedGoogle Scholar
  60. 60.
    Liu X, Kim CN, Yang J, Jemmerson R, Wang X (1996) Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86:147CrossRefPubMedGoogle Scholar
  61. 61.
    Longley DB, Johnston PG (2005) Molecular mechanisms of drug resistance. J Pathol 205:275CrossRefPubMedGoogle Scholar
  62. 62.
    Luo X, Budihardjo I, Zou H, Slaughter C, Wang X (1998) Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 94:481CrossRefPubMedGoogle Scholar
  63. 63.
    Meijer AJ, Codogno P (2004) Regulation and role of autophagy in mammalian cells. Int J Biochem Cell Biol 36:2445CrossRefPubMedGoogle Scholar
  64. 64.
    Mihara M, Erster S, Zaika A, Petrenko O, Chittenden T, Pancoska P, Moll UM (2003) p53 has a direct apoptogenic role at the mitochondria. Mol Cell 11:577CrossRefPubMedGoogle Scholar
  65. 65.
    Mizushima N, Ohsumi Y, Yoshimori T (2002) Autophagosome formation in mammalian cells. Cell Struct Funct 27:421CrossRefPubMedGoogle Scholar
  66. 66.
    Nutt LK, Gogvadze V, Uthaisang W, Mirnikjoo B, McConkey DJ, Orrenius S (2005) Indirect effects of Bax and Bak initiate the mitochondrial alterations that lead to Cytochrome c release during arsenic trioxide-induced apoptosis. Cancer Biol Ther 4 (Epub ahead of print)Google Scholar
  67. 67.
    Nutt LK, Pataer A, Pahler J, Fang B, Roth J, McConkey DJ, Swisher SG (2002) Bax and Bak promote apoptosis by modulating endoplasmic reticular and mitochondrial Ca2+ stores. J Biol Chem 277:9219CrossRefPubMedGoogle Scholar
  68. 68.
    O’Connor L, Strasser A, O’Reilly LA, Hausmann G, Adams JM, Cory S, Huang DC (1998) Bim: a novel member of the Bcl-2 family that promotes apoptosis. EMBO J 17:384CrossRefPubMedGoogle Scholar
  69. 69.
    Oakes SA, Opferman JT, Pozzan T, Korsmeyer SJ, Scorrano L (2003) Regulation of endoplasmic reticulum Ca2+ dynamics by proapoptotic BCL-2 family members. Biochem Pharmacol 66:1335CrossRefPubMedGoogle Scholar
  70. 70.
    Oakes SA, Scorrano L, Opferman JT, Bassik MC, Nishino M, Pozzan T, Korsmeyer SJ (2005) Proapoptotic BAX and BAK regulate the type 1 inositol trisphosphate receptor and calcium leak from the endoplasmic reticulum. Proc Natl Acad Sci USA 102:105CrossRefPubMedGoogle Scholar
  71. 71.
    Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, Tokino T, Taniguchi T, Tanaka N (2000) Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science 288:1053CrossRefPubMedGoogle Scholar
  72. 72.
    Oltvai ZN, Milliman CL, Korsmeyer SJ (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74:609CrossRefPubMedGoogle Scholar
  73. 73.
    Oyadomari S, Mori M (2004) Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ 11:381CrossRefPubMedGoogle Scholar
  74. 74.
    Paquet C, Schmitt E, Beauchemin M, Bertrand R (2004) Activation of multidomain and BH3-only pro-apoptotic Bcl-2 family members in p53-defective cells. Apoptosis 9:815CrossRefPubMedGoogle Scholar
  75. 75.
    Pavlov EV, Priault M, Pietkiewicz D, Cheng EH, Antonsson B, Manon S, Korsmeyer SJ, Mannella CA, Kinnally KW (2001) A novel, high conductance channel of mitochondria linked to apoptosis in mammalian cells and Bax expression in yeast. J Cell Biol 155:725CrossRefPubMedGoogle Scholar
  76. 76.
    Pelicano H, Carney D, Huang P (2004) ROS stress in cancer cells and therapeutic implications. Drug Resist Updat 7:97CrossRefPubMedGoogle Scholar
  77. 77.
    Pinton P, Ferrari D, Rapizzi E, Di Virgilio F, Pozzan T, Rizzuto R (2001) The Ca2+ concentration of the endoplasmic reticulum is a key determinant of ceramide-induced apoptosis: significance for the molecular mechanism of Bcl-2 action. EMBO J 20:2690CrossRefPubMedGoogle Scholar
  78. 78.
    Puthalakath Ha, Strasser A (2002) Keeping killers on a tight leash: transcriptional and post-translational control of the pro-apoptotic activity of BH3-only proteins. Cell Death Differ 9:505CrossRefPubMedGoogle Scholar
  79. 79.
    Rizzuto R, Pinton P, Ferrari D, Chami M, Szabadkai G, Magalhaes PJ, Di Virgilio F, Pozzan T (2003) Calcium and apoptosis: facts and hypotheses. Oncogene 22:8619CrossRefPubMedGoogle Scholar
  80. 80.
    Ron D (2002) Translational control in the endoplasmic reticulum stress response. J Clin Invest 110:1383CrossRefPubMedGoogle Scholar
  81. 81.
    Rutkowski DT, Kaufman RJ (2004) A trip to the ER: coping with stress. Trends Cell Biol 14:20CrossRefPubMedGoogle Scholar
  82. 82.
    Scholz C, Wieder T, Starck L, Essmann F, Schulze-Osthoff K, Dorken B, Daniel PT (2005) Arsenic trioxide triggers a regulated form of caspase-independent necrotic cell death via the mitochondrial death pathway. Oncogene 24:1904CrossRefPubMedGoogle Scholar
  83. 83.
    Schroder M, Kaufman RJ (2005) ER stress and the unfolded protein response. Mutat Res 569:29PubMedGoogle Scholar
  84. 84.
    Scorrano L, Oakes SA, Opferman JT, Cheng EH, Sorcinelli MD, Pozzan T, Korsmeyer SJ (2003) BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis. Science 300:135CrossRefPubMedGoogle Scholar
  85. 85.
    Shimizu S, Matsuoka Y, Shinohara Y, Yoneda Y, Tsujimoto Y (2001) Essential role of voltage-dependent anion channel in various forms of apoptosis in mammalian cells. J Cell Biol 152:237CrossRefPubMedGoogle Scholar
  86. 86.
    Shimizu S, Narita M, Tsujimoto Y (1999) Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Nature 399:483CrossRefPubMedGoogle Scholar
  87. 87.
    Shintani T, Klionsky DJ (2004) Autophagy in health and disease: a double-edged sword. Science 306:990CrossRefPubMedGoogle Scholar
  88. 88.
    Smaili SS, Hsu YT, Youle RJ, Russell JT (2000) Mitochondria in Ca2+ signaling and apoptosis. J Bioenerg Biomembr 32:35CrossRefPubMedGoogle Scholar
  89. 89.
    Sugiyama T, Shimizu S, Matsuoka Y, Yoneda Y, Tsujimoto Y (2002) Activation of mitochondrial voltage-dependent anion channel by apro-apoptotic BH3-only protein Bim. Oncogene 21:4944CrossRefPubMedGoogle Scholar
  90. 90.
    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 397:441CrossRefPubMedGoogle Scholar
  91. 91.
    Szalai G, Krishnamurthy R, Hajnoczky G (1999) Apoptosis driven by IP(3)-linked mitochondrial calcium signals. EMBO J 18:6349CrossRefPubMedGoogle Scholar
  92. 92.
    Thorburn J, Moore F, Rao A, Barclay WW, Thomas LR, Grant KW, Cramer SD, Thorburn A (2005) Selective inactivation of a Fas-associated death domain protein (FADD)-dependent apoptosis and autophagy pathway in immortal epithelial cells. Mol Biol Cell 16:1189CrossRefPubMedGoogle Scholar
  93. 93.
    Tsujimoto Y (2003) Cell death regulation by the Bcl-2 protein family in the mitochondria. J Cell Physiol 195:158CrossRefPubMedGoogle Scholar
  94. 94.
    Tsujimoto Y, Finger LR, Yunis J, Nowell PC, Croce CM (1984) Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science 226:1097PubMedGoogle Scholar
  95. 95.
    Turk V, Turk B, Turk D (2001) Lysosomal cysteine proteases: facts and opportunities. EMBO J 20:4629CrossRefPubMedGoogle Scholar
  96. 96.
    Verrier F, Deniaud A, Lebras M, Metivier D, Kroemer G, Mignotte B, Jan G, Brenner C (2004) Dynamic evolution of the adenine nucleotide translocase interactome during chemotherapy-induced apoptosis. Oncogene 23:8049CrossRefPubMedGoogle Scholar
  97. 97.
    Villunger A, Michalak EM, Coultas L, Mullauer F, Bock G, Ausserlechner MJ, Adams JM, Strasser A (2003) p53- and drug-induced apoptotic responses mediated by BH3-only proteins puma and noxa. Science 302:1036CrossRefPubMedGoogle Scholar
  98. 98.
    Vyssokikh MY, Brdiczka D (2003) The function of complexes between the outer mitochondrial membrane pore (VDAC) and the adenine nucleotide translocase in regulation of energy metabolism and apoptosis. Acta Biochim Pol 50:389PubMedGoogle Scholar
  99. 99.
    Wang XZ, Kuroda M, Sok J, Batchvarova N, Kimmel R, Chung P, Zinszner H, Ron D (1998) Identification of novel stress-induced genes downstream of chop. EMBO J 17:3619CrossRefPubMedGoogle Scholar
  100. 100.
    Wei MC, Zong WX, Cheng EH, Lindsten T, Panoutsakopoulou V, Ross AJ, Roth KA, MacGregor GR, Thompson CB, Korsmeyer SJ (2001) Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292:727CrossRefPubMedGoogle Scholar
  101. 101.
    Yang E, Zha J, Jockel J, Boise LH, Thompson CB, Korsmeyer SJ (1995) Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death. Cell 80:285CrossRefPubMedGoogle Scholar
  102. 102.
    Yoshimori T (2004) Autophagy: a regulated bulk degradation process inside cells. Biochem Biophys Res Commun 313:453CrossRefPubMedGoogle Scholar
  103. 103.
    Yu J, Zhang L, Hwang PM, Kinzler KW, Vogelstein B (2001) PUMA induces the rapid apoptosis of colorectal cancer cells. Mol Cell 7:673CrossRefPubMedGoogle Scholar
  104. 104.
    Zha J, Weiler S, Oh KJ, Wei MC, Korsmeyer SJ (2000) Posttranslational N-myristoylation of BID as a molecular switch for targeting mitochondria and apoptosis. Science 290:1761CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.International Radiation Information Center, Research Institute for Radiation Biology and MedicineHiroshima UniversityHiroshimaJapan
  2. 2.Depertment of Surgical Oncology, Research Institute for Radiation Biology and MedicineHiroshima UniversityHiroshimaJapan

Personalised recommendations