Mitochondria have long been known to be critical for cell survival due to their role in energy metabolism. However, not until the mid-1990s did it become evident that mitochondria are also active participants in programmed cell death (PCD). This chapter focuses mainly on the role the mitochondria in mammalian cell death and cancer progression and therapy.
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References
Abe, K., Kurakin, A., Mohseni-Maybodi, M., Kay, B., and Khosravi-Far, R. (2000). The complexity of TNF-related apoptosis-inducing ligand. Ann N Y Acad Sci 926, 52–63.
Acehan, D., Jiang, X., Morgan, D. G., Heuser, J. E., Wang, X., and Akey, C. W. (2002). Three-dimensional structure of the apoptosome: implications for assembly, procaspase-9 binding, and activation. Mol Cell 9, 423–432.
Adams, J. M. and Cory, S. (2002). Apoptosomes: engines for caspase activation. Curr Opin Cell Biol 14, 715–720.
Adrain, C., Slee, E. A., Harte, M. T., and Martin, S. J. (1999). Regulation of apoptotic protease activating factor-1 oligomerization and apoptosis by the WD-40 repeat region. J Biol Chem 274, 20855–20860.
Adrain, C., Creagh, E. M., and Martin, S. J. (2001). Apoptosis-associated release of Smac/DIABLO from mitochondria requires active caspases and is blocked by bcl-2. Embo J 20, 6627–6636.
Algeciras-Schimnich, A., Shen, L., Barnhart, B. C., Murmann, A. E., Burkhardt, J. K., and Peter, M. E. (2002). Molecular ordering of the initial signaling events of CD95. Mol Cell Biol 22, 207–220.
Andreyev, A. Y., Kushnareva, Y. E., and Starkov, A. A. (2005). Mitochondrial metabolism of reactive oxygen species. Biochemistry (Mosc) 70, 200–214.
Antonsson, B., Conti, F., Ciavatta, A., Montessuit, S., Lewis, S., Martinou, I., Bernasconi, L., Bernard, A., Mermod, J. J., Mazzei, G., et al. (1997). Inhibition of bax channel-forming activity by bcl-2. Science 277, 370–372.
Arnoult, D., Gaume, B., Karbowski, M., Sharpe, J. C., Cecconi, F., and Youle, R. J. (2003). Mitochondrial release of AIF and EndoG requires caspase activation downstream of bax/bak-mediated permeabilization. Embo J 22, 4385–4399.
Ashkenazi, A. and Dixit, V. M. (1999). Apoptosis control by death and decoy receptors. Curr Opin Cell Biol 11, 255–260.
Baliga, B. and Kumar, S. (2003). Apaf-1/cytochrome c apoptosome: an essential initiator of caspase activation or just a sideshow? Cell Death Differ 10, 16–18.
Barnhart, B. C., Legembre, P., Pietras, E., Bubici, C., Franzoso, G., and Peter, M. E. (2004). CD95 ligand induces motility and invasiveness of apoptosis-resistant tumor cells. Embo J 23, 3175–3185.
Bettaieb, A., Dubrez-Daloz, L., Launay, S., Plenchette, S., Rebe, C., Cathelin, S., and Solary, E. (2003). Bcl-2 proteins: targets and tools for chemosensitisation of tumor cells. Curr Med Chem Anti-Canc Agents 3, 307–318.
Beyer, R. E. (1992). An analysis of the role of coenzyme Q in free radical generation and as an antioxidant. Biochem Cell Biol 70, 390–403.
Brenner, C., Cadiou, H., Vieira, H. L., Zamzami, N., Marzo, I., Xie, Z., Leber, B., Andrews, D., Duclohier, H., Reed, J. C., and Kroemer, G. (2000). Bcl-2 and bax regulate the channel activity of the mitochondrial adenine nucleotide translocator. Oncogene 19, 329–336.
Brenner, C., Le Bras, M., and Kroemer, G. (2003). Insights into the mitochondrial signaling pathway: what lessons for chemotherapy? J Clin Immunol 23, 73–80.
Burns, T. F. and el-Deiry, W. S. (2003). Cell death signaling in malignancy. Cancer Treat Res 115, 319–343.
Cain, K., Bratton, S. B., and Cohen, G. M. (2002). The apaf-1 apoptosome: a large caspase-activating complex. Biochimie 84, 203–214.
Cande, C., Cecconi, F., Dessen, P., and Kroemer, G. (2002). Apoptosis-inducing factor (AIF): key to the conserved caspase-independent pathways of cell death? J Cell Sci 115, 4727–4734.
Carew, J. S. and Huang, P. (2002). Mitochondrial defects in cancer. Mol Cancer 1, 9.
Cecconi, F., Alvarez-Bolado, G., Meyer, B. I., Roth, K. A., and Gruss, P. (1998). Apaf1 (CED-4 homolog) regulates programmed cell death in mammalian development. Cell 94, 727–737.
Chao, D. T. and Korsmeyer, S. J. (1998). BCL-2 family: regulators of cell death. Annu Rev Immunol 16, 395–419.
Cheng, E. H., Wei, M. C., Weiler, S., Flavell, R. A., Mak, T. W., Lindsten, T., and Korsmeyer, S. J. (2001). BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol Cell 8, 705–711.
Chinnaiyan, A. M. (1999). The apoptosome: heart and soul of the cell death machine. Neoplasia 1, 5–15.
Chou, J. J., Li, H., Salvesen, G. S., Yuan, J., and Wagner, G. (1999). Solution structure of BID, an intracellular amplifier of apoptotic signaling. Cell 96, 615–624.
Colombini, M., Blachly-Dyson, E., and Forte, M. (1996). VDAC, a channel in the outer mitochondrial membrane. Ion Channels 4, 169–202.
Cory, S. and Adams, J. M. (2002). The bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2, 647–656.
Cory, S., Huang, D. C., and Adams, J. M. (2003). The bcl-2 family: roles in cell survival and oncogenesis. Oncogene 22, 8590–8607.
Costantini, P., Jacotot, E., Decaudin, D., and Kroemer, G. (2000). Mitochondrion as a novel target of anticancer chemotherapy. J Natl Cancer Inst 92, 1042–1053.
Cote, J. and Ruiz-Carrillo, A. (1993). Primers for mitochondrial DNA replication generated by endonuclease G. Science 261, 765–769.
Crompton, M. (1999). The mitochondrial permeability transition pore and its role in cell death. Biochem J 341 (Pt 2), 233–249.
Danial, N. N. and Korsmeyer, S. J. (2004). Cell death: critical control points. Cell 116, 205–219.
Daniel, P. T., Wieder, T., Sturm, I., and Schulze-Osthoff, K. (2001). The kiss of death: promises and failures of death receptors and ligands in cancer therapy. Leukemia 15, 1022–1032.
Debatin, K. M., Poncet, D., and Kroemer, G. (2002). Chemotherapy: targeting the mitochondrial cell death pathway. Oncogene 21, 8786–8803.
Degli Esposti, M. (1999). To die or not to die–the quest of the TRAIL receptors. J Leukoc Biol 65, 535–542.
Dejean, L. M., Martinez-Caballero, S., Guo, L., Hughes, C., Teijido, O., Ducret, T., Ichas, F., Korsmeyer, S. J., Antonsson, B., Jonas, E. A., and Kinnally, K. W. (2005). Oligomeric bax is a component of the putative cytochrome c release channel MAC, mitochondrial apoptosis-induced channel. Mol Biol Cell 16, 2424–2432.
Dejean, L. M., Martinez-Caballero, S., and Kinnally, K. W. (2006). Is MAC the knife that cuts cytochrome c from mitochondria during apoptosis? Cell Death Differ 13, 1387–1395.
Deveraux, Q. L. and Reed, J. C. (1999). IAP family proteins–suppressors of apoptosis. Genes Dev 13, 239–252.
Dias, N. and Bailly, C. (2005). Drugs targeting mitochondrial functions to control tumor cell growth. Biochem Pharmacol 70, 1–12.
Diekert, K., de Kroon, A. I., Kispal, G., and Lill, R. (2001). Isolation and subfractionation of mitochondria from the yeast Saccharomyces cerevisiae. Methods Cell Biol 65, 37–51.
Dumont, M. E., Cardillo, T. S., Hayes, M. K., and Sherman, F. (1991). Role of cytochrome c heme lyase in mitochondrial import and accumulation of cytochrome c in Saccharomyces cerevisiae. Mol Cell Biol 11, 5487–5496.
Ekert, P. G., Silke, J., Hawkins, C. J., Verhagen, A. M., and Vaux, D. L. (2001). DIABLO promotes apoptosis by removing MIHA/XIAP from processed caspase 9. J Cell Biol 152, 483–490.
el-Deiry, W. S. (1997). Role of oncogenes in resistance and killing by cancer therapeutic agents. Curr Opin Oncol 9, 79–87.
Eskes, R., Desagher, S., Antonsson, B., and Martinou, J. C. (2000). Bid induces the oligomerization and insertion of bax into the outer mitochondrial membrane. Mol Cell Biol 20, 929–935.
Esposti, M. D., Cristea, I. M., Gaskell, S. J., Nakao, Y., and Dive, C. (2003). Proapoptotic bid binds to monolysocardiolipin, a new molecular connection between mitochondrial membranes and cell death. Cell Death Differ.
Fantin, V. R. and Leder, P. (2006). Mitochondriotoxic compounds for cancer therapy. Oncogene 25, 4787–4797.
Fiers, W., Beyaert, R., Declercq, W., and Vandenabeele, P. (1999). More than one way to die: apoptosis, necrosis and reactive oxygen damage. Oncogene 18, 7719–7730.
Fliss, M. S., Usadel, H., Caballero, O. L., Wu, L., Buta, M. R., Eleff, S. M., Jen, J., and Sidransky, D. (2000). Facile detection of mitochondrial DNA mutations in tumors and bodily fluids. Science 287, 2017–2019.
Galluzzi, L., Larochette, N., Zamzami, N., and Kroemer, G. (2006). Mitochondria as therapeutic targets for cancer chemotherapy. Oncogene 25, 4812–4830.
Geske, F. J. and Gerschenson, L. E. (2001). The biology of apoptosis. Hum Pathol 32, 1029–1038.
Green, D. R. and Evan, G. I. (2002). A matter of life and death. Cancer Cell 1, 19–30.
Green, D. R. and Kroemer, G. (2004). The pathophysiology of mitochondrial cell death. Science 305, 626–629.
Guihard, G., Bellot, G., Moreau, C., Pradal, G., Ferry, N., Thomy, R., Fichet, P., Meflah, K., and Vallette, F. M. (2004). The mitochondrial apoptosis-induced channel (MAC) corresponds to a late apoptotic event. J Biol Chem 279, 46542–46550.
Guo, L., Pietkiewicz, D., Pavlov, E. V., Grigoriev, S. M., Kasianowicz, J. J., Dejean, L. M., Korsmeyer, S. J., Antonsson, B., and Kinnally, K. W. (2004). Effects of cytochrome c on the mitochondrial apoptosis-induced channel MAC. Am J Physiol Cell Physiol 286, C1109–1117.
Hanahan, D. and Weinberg, R. A. (2000). The hallmarks of cancer. Cell 100, 57–70.
Hansen, T. M., Smith, D. J., and Nagley, P. (2006). Smac/DIABLO is not released from mitochondria during apoptotic signalling in cells deficient in cytochrome c. Cell Death Differ 13, 1181–1190.
Hegde, R., Srinivasula, S. M., Zhang, Z., Wassell, R., Mukattash, R., Cilenti, L., DuBois, G., Lazebnik, Y., Zervos, A. S., Fernandes-Alnemri, T., and Alnemri, E. S. (2002). Identification of Omi/HtrA2 as a mitochondrial apoptotic serine protease that disrupts inhibitor of apoptosis protein-caspase interaction. J Biol Chem 277, 432–438.
Hersey, P. and Zhang, X. D. (2003). Overcoming resistance of cancer cells to apoptosis. J Cell Physiol 196, 9–18.
Hill, M. M., Adrain, C., and Martin, S. J. (2003). Portrait of a killer: the mitochondrial apoptosome emerges from the shadows. Mol Interv 3, 19–26.
Jaattela, M. (2004). Multiple cell death pathways as regulators of tumour initiation and progression. Oncogene 23, 2746–2756.
Kasibhatla, S. and Tseng, B. (2003). Why target apoptosis in cancer treatment? Mol Cancer Ther 2, 573–580.
Khosravi-Far, R. and Esposti, M. D. (2004). Death receptor signals to mitochondria. Cancer Biol Ther 3, 1051–1057.
Kim, R., Emi, M., Tanabe, K., and Toge, T. (2004). Therapeutic potential of antisense Bcl-2 as a chemosensitizer for cancer therapy. Cancer 101, 2491–2502.
Kluck, R. M., Bossy-Wetzel, E., Green, D. R., and Newmeyer, D. D. (1997). The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science 275, 1132–1136.
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., and Newmeyer, D. D. (1999). 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, 809–822.
Kluza, J., Gallego, M. A., Loyens, A., Beauvillain, J. C., Sousa-Faro, J. M., Cuevas, C., Marchetti, P., and Bailly, C. (2006). Cancer cell mitochondria are direct proapoptotic targets for the marine antitumor drug lamellarin D. Cancer Res 66, 3177–3187.
Korsmeyer, S. J., Wei, M. C., Saito, M., Weiler, S., Oh, K. J., and Schlesinger, P. H. (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, 1166–1173.
Kroemer, G. (2003). Mitochondrial control of apoptosis: an introduction. Biochem Biophys Res Commun 304, 433–435.
Kuwana, T. and Newmeyer, D. D. (2003). Bcl-2-family proteins and the role of mitochondria in apoptosis. Curr Opin Cell Biol 15, 691–699.
Kuwana, T., Smith, J. J., Muzio, M., Dixit, V., Newmeyer, D. D., and Kornbluth, S. (1998). Apoptosis induction by caspase-8 is amplified through the mitochondrial release of cytochrome c. J Biol Chem 273, 16589–16594.
Kuwana, T., Mackey, M. R., Perkins, G., Ellisman, M. H., Latterich, M., Schneiter, R., Green, D. R., and Newmeyer, D. D. (2002). Bid, bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane. Cell 111, 331–342.
Lawen, A. (2003). Apoptosis-an introduction. Bioessays 25, 888–896.
Li, H., Zhu, H., Xu, C. J., and Yuan, J. (1998). Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94, 491–501.
Li, L. Y., Luo, X., and Wang, X. (2001). Endonuclease G is an apoptotic DNase when released from mitochondria. Nature 412, 95–99.
Lim, M. L., Minamikawa, T., and Nagley, P. (2001). The protonophore CCCP induces mitochondrial permeability transition without cytochrome c release in human osteosarcoma cells. FEBS Lett 503, 69–74.
Lo, S., Tolner, B., Taanman, J. W., Cooper, J. M., Gu, M., Hartley, J. A., Schapira, A. H., and Hochhauser, D. (2005). Assessment of the significance of mitochondrial DNA damage by chemotherapeutic agents. Int J Oncol 27, 337–344.
Lorenzo, H. K., Susin, S. A., Penninger, J., and Kroemer, G. (1999). Apoptosis inducing factor (AIF): a phylogenetically old, caspase-independent effector of cell death. Cell Death Differ 6, 516–524.
Luo, X., Budihardjo, I., Zou, H., Slaughter, C., and 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, 481–490.
Lutter, M., Fang, M., Luo, X., Nishijima, M., Xie, X., and Wang, X. (2000). Cardiolipin provides specificity for targeting of tBid to mitochondria. Nat Cell Biol 2, 754–761.
Mangan, P. S. and Colombini, M. (1987). Ultrasteep voltage dependence in a membrane channel. Proc Natl Acad Sci USA 84, 4896–4900.
Martinou, J. C. and Green, D. R. (2001). Breaking the mitochondrial barrier. Nat Rev Mol Cell Biol 2, 63–67.
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., and Downward, J. (2002). The serine protease Omi/HtrA2 regulates apoptosis by binding XIAP through a reaper-like motif. J Biol Chem 277, 439–444.
Marzo, I., Brenner, C., and Kroemer, G. (1998a). The central role of the mitochondrial megachannel in apoptosis: evidence obtained with intact cells, isolated mitochondria, and purified protein complexes. Biomed Pharmacother 52, 248–251.
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., and Kroemer, G. (1998b). Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis. Science 281, 2027–2031.
Mayer, A., Neupert, W., and Lill, R. (1995). Translocation of apocytochrome c across the outer membrane of mitochondria. J Biol Chem 270, 12390–12397.
McDonnell, J. M., Fushman, D., Milliman, C. L., Korsmeyer, S. J., and Cowburn, D. (1999). Solution structure of the proapoptotic molecule BID: a structural basis for apoptotic agonists and antagonists. Cell 96, 625–634.
McMillin, J. B. and Dowhan, W. (2002). Cardiolipin and apoptosis. Biochim Biophys Acta 1585, 97–107.
Miller, L. K. (1999). An exegesis of IAPs: salvation and surprises from BIR motifs. Trends Cell Biol 9, 323–328.
Miramar, M. D., Costantini, P., Ravagnan, L., Saraiva, L. M., Haouzi, D., Brothers, G., Penninger, J. M., Peleato, M. L., Kroemer, G., and Susin, S. A. (2001). NADH oxidase activity of mitochondrial apoptosis-inducing factor. J Biol Chem 276, 16391–16398.
Morisaki, T. and Katano, M. (2003). Mitochondria-targeting therapeutic strategies for overcoming chemoresistance and progression of cancer. Curr Med Chem 10, 2517–2521.
Nechushtan, A., Smith, C. L., Lamensdorf, I., Yoon, S. H., and Youle, R. J. (2001). Bax and Bak coalesce into novel mitochondria-associated clusters during apoptosis. J Cell Biol 153, 1265–1276.
Newmeyer, D. D. and Ferguson-Miller, S. (2003). Mitochondria: releasing power for life and unleashing the machineries of death. Cell 112, 481–490.
O’Neill, J., Manion, M., Schwartz, P., and Hockenbery, D. M. (2004). Promises and challenges of targeting Bcl-2 anti-apoptotic proteins for cancer therapy. Biochim Biophys Acta 1705, 43–51.
Ohtsuka, T., Nishijima, M., Suzuki, K., and Akamatsu, Y. (1993). Mitochondrial dysfunction of a cultured Chinese hamster ovary cell mutant deficient in cardiolipin. J Biol Chem 268, 22914–22919.
Ozoren, N. and El-Deiry, W. S. (2002). Defining characteristics of types I and II apoptotic cells in response to TRAIL. Neoplasia 4, 551–557.
Ozoren, N. and El-Deiry, W. S. (2003). Cell surface Death Receptor signaling in normal and cancer cells. Semin Cancer Biol 13, 135–147.
Pavlov, E. V., Priault, M., Pietkiewicz, D., Cheng, E. H., Antonsson, B., Manon, S., Korsmeyer, S. J., Mannella, C. A., and Kinnally, K. W. (2001). A novel, high conductance channel of mitochondria linked to apoptosis in mammalian cells and Bax expression in yeast. J Cell Biol 155, 725–731.
Penninger, J. M. and Kroemer, G. (2003). Mitochondria, AIF and caspases–rivaling for cell death execution. Nat Cell Biol 5, 97–99.
Peter, M. E. and Krammer, P. H. (1998). Mechanisms of CD95 (APO-1/Fas)-mediated apoptosis. Curr Opin Immunol 10, 545–551.
Peter, M. E. and Krammer, P. H. (2003). The CD95(APO-1/Fas) DISC and beyond. Cell Death Differ 10, 26–35.
Raha, S. and Robinson, B. H. (2000). Mitochondria, oxygen free radicals, disease and ageing. Trends Biochem Sci 25, 502–508.
Ravagnan, L., Roumier, T., and Kroemer, G. (2002). Mitochondria, the killer organelles and their weapons. J Cell Physiol 192, 131–137.
Reed, J. C. (2004). Apoptosis mechanisms: implications for cancer drug discovery. Oncology (Williston Park) 18, 11–20.
Rehm, M., Dussmann, H., and Prehn, J. H. (2003). Real-time single cell analysis of Smac/DIABLO release during apoptosis. J Cell Biol 162, 1031–1043.
Rotem, R., Heyfets, A., Fingrut, O., Blickstein, D., Shaklai, M., and Flescher, E. (2005). Jasmonates: novel anticancer agents acting directly and selectively on human cancer cell mitochondria. Cancer Res 65, 1984–1993.
Saelens, X., Festjens, N., Vande Walle, L., van Gurp, M., van Loo, G., and Vandenabeele, P. (2004). Toxic proteins released from mitochondria in cell death. Oncogene 23, 2861–2874.
Saito, S., Hiroi, Y., Zou, Y., Aikawa, R., Toko, H., Shibasaki, F., Yazaki, Y., Nagai, R., and Komuro, I. (2000). beta-Adrenergic pathway induces apoptosis through calcineurin activation in cardiac myocytes. J Biol Chem 275, 34528–34533.
Salvesen, G. S. and Dixit, V. M. (1997). Caspases: intracellular signaling by proteolysis. Cell 91, 443–446.
Salvesen, G. S. and Renatus, M. (2002). Apoptosome: the seven-spoked death machine. Dev Cell 2, 256–257.
Schatz, G. (1995). Mitochondria: beyond oxidative phosphorylation. Biochim Biophys Acta 1271, 123–126.
Schendel, S. L., Xie, Z., Montal, M. O., Matsuyama, S., Montal, M., and Reed, J. C. (1997). Channel formation by antiapoptotic protein Bcl-2. Proc Natl Acad Sci USA 94, 5113–5118.
Schlame, M., Rua, D., and Greenberg, M. L. (2000). The biosynthesis and functional role of cardiolipin. Prog Lipid Res 39, 257–288.
Schulze-Osthoff, K., Ferrari, D., Los, M., Wesselborg, S., and Peter, M. E. (1998). Apoptosis signaling by death receptors. Eur J Biochem 254, 439–459.
Semenza, G. L., Artemov, D., Bedi, A., Bhujwalla, Z., Chiles, K., Feldser, D., Laughner, E., Ravi, R., Simons, J., Taghavi, P., and Zhong, H. (2001). The metabolism of tumours: 70 years later. Novartis Found Symp 240, 251–260; discussion 260–254.
Shangary, S. and Johnson, D. E. (2003). Recent advances in the development of anticancer agents targeting cell death inhibitors in the Bcl-2 protein family. Leukemia 17, 1470–1481.
Sheikh, M. S. and Huang, Y. (2004). Death receptors as targets of cancer therapeutics. Curr Cancer Drug Targets 4, 97–104.
Shi, Y. (2002). Apoptosome: the cellular engine for the activation of caspase-9. Structure (Camb) 10, 285–288.
Shidoji, Y., Hayashi, K., Komura, S., Ohishi, N., and Yagi, K. (1999). Loss of molecular interaction between cytochrome c and cardiolipin due to lipid peroxidation. Biochem Biophys Res Commun 264, 343–347.
Sies, H. and de Groot, H. (1992). Role of reactive oxygen species in cell toxicity. Toxicol Lett 64–65 Spec No, 547–551.
Singh, K. K., Russell, J., Sigala, B., Zhang, Y., Williams, J., and Keshav, K. F. (1999). Mitochondrial DNA determines the cellular response to cancer therapeutic agents. Oncogene 18, 6641–6646.
Slee, E. A., Adrain, C., and Martin, S. J. (1999). Serial killers: ordering caspase activation events in apoptosis. Cell Death Differ 6, 1067–1074.
Soengas, M. S., Alarcon, R. M., Yoshida, H., Giaccia, A. J., Hakem, R., Mak, T. W., and Lowe, S. W. (1999). Apaf-1 and caspase-9 in p53-dependent apoptosis and tumor inhibition. Science 284, 156–159.
Sorice, M., Circella, A., Cristea, I. M., Garofalo, T., Renzo, L. D., Alessandri, C., Valesini, G., and Esposti, M. D. (2004). Cardiolipin and its metabolites move from mitochondria to other cellular membranes during death receptor-mediated apoptosis. Cell Death Differ 11, 1133–1145.
Springs, S. L., Diavolitsis, V. M., Goodhouse, J., and McLendon, G. L. (2002). The kinetics of translocation of Smac/DIABLO from the mitochondria to the cytosol in HeLa cells. J Biol Chem 277, 45715–45718.
Srinivasula, S. M., Ahmad, M., Guo, Y., Zhan, Y., Lazebnik, Y., Fernandes-Alnemri, T., and Alnemri, E. S. (1999). Identification of an endogenous dominant-negative short isoform of caspase-9 that can regulate apoptosis. Cancer Res 59, 999–1002.
Stegh, A. H. and Peter, M. E. (2001). Apoptosis and caspases. Cardiol Clin 19, 13–29.
Strasser, A., O’Connor, L., and Dixit, V. M. (2000). Apoptosis signaling. Annu Rev Biochem 69, 217–245.
Susin, S. A., Lorenzo, H. K., Zamzami, N., Marzo, I., Snow, B. E., Brothers, G. M., Mangion, J., Jacotot, E., Costantini, P., Loeffler, M., et al. (1999). Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397, 441–446.
Suzuki, Y., Imai, Y., Nakayama, H., Takahashi, K., Takio, K., and Takahashi, R. (2001). A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death. Mol Cell 8, 613–621.
Suzuki, Y., Takahashi-Niki, K., Akagi, T., Hashikawa, T., and Takahashi, R. (2004). Mitochondrial protease Omi/HtrA2 enhances caspase activation through multiple pathways. Cell Death Differ 11, 208–216.
Szeto, H. H. (2006). Cell-permeable, mitochondrial-targeted, peptide antioxidants. Aaps J 8, E277–283.
Thomas, L., Blachly-Dyson, E., Colombini, M., and Forte, M. (1993). Mapping of residues forming the voltage sensor of the voltage-dependent anion-selective channel. Proc Natl Acad Sci USA 90, 5446–5449.
Thompson, C. B. (1995). Apoptosis in the pathogenesis and treatment of disease. Science 267, 1456–1462.
Thorburn, A. (2004). Death receptor-induced cell killing. Cell Signal 16, 139–144.
van Loo, G., Schotte, P., van Gurp, M., Demol, H., Hoorelbeke, B., Gevaert, K., Rodriguez, I., Ruiz-Carrillo, A., Vandekerckhove, J., Declercq, W., et al. (2001). Endonuclease G: a mitochondrial protein released in apoptosis and involved in caspase-independent DNA degradation. Cell Death Differ 8, 1136–1142.
Vaux, D. L. and Korsmeyer, S. J. (1999). Cell death in development. Cell 96, 245–254.
Verhagen, A. M. and Vaux, D. L. (2002). Cell death regulation by the mammalian IAP antagonist Diablo/Smac. Apoptosis 7, 163–166.
Vieira, H. L., Belzacq, A. S., Haouzi, D., Bernassola, F., Cohen, I., Jacotot, E., Ferri, K. F., El Hamel, C., Bartle, L. M., Melino, G., et al. (2001). The adenine nucleotide translocator: a target of nitric oxide, peroxynitrite, and 4-hydroxynonenal. Oncogene 20, 4305–4316.
Walensky, L. D. (2006). BCL-2 in the crosshairs: tipping the balance of life and death. Cell Death Differ 13, 1339–1350.
Wallach, D. (1997). Apoptosis. Placing death under control. Nature 388, 123, 125–126.
Wang, K., Yin, X. M., Chao, D. T., Milliman, C. L., and Korsmeyer, S. J. (1996). BID: a novel BH3 domain-only death agonist. Genes Dev 10, 2859–2869.
Warburg, E. (1951). Therapeutic imperative and evaluation of therapeutics. Ugeskr Laeger 113, 86–88.
Waterhouse, N. J., Goldstein, J. C., Kluck, R. M., Newmeyer, D. D., and Green, D. R. (2001). The (Holey) study of mitochondria in apoptosis. Methods Cell Biol 66, 365–391.
Wei, M. C., Lindsten, T., Mootha, V. K., Weiler, S., Gross, A., Ashiya, M., Thompson, C. B., and Korsmeyer, S. J. (2000). tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c. Genes Dev 14, 2060–2071.
Wei, M. C., Zong, W. X., Cheng, E. H., Lindsten, T., Panoutsakopoulou, V., Ross, A. J., Roth, K. A., MacGregor, G. R., Thompson, C. B., and Korsmeyer, S. J. (2001). Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292, 727–730.
Wright, M. M., Howe, A. G., and Zaremberg, V. (2004). Cell membranes and apoptosis: role of cardiolipin, phosphatidylcholine, and anticancer lipid analogues. Biochem Cell Biol 82, 18–26.
Yang, J., Liu, X., Bhalla, K., Kim, C. N., Ibrado, A. M., Cai, J., Peng, T. I., Jones, D. P., and Wang, X. (1997). Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science 275, 1129–1132.
Yang, X., Fraser, M., Moll, U. M., Basak, A., and Tsang, B. K. (2006). Akt-mediated cisplatin resistance in ovarian cancer: modulation of p53 action on caspase-dependent mitochondrial death pathway. Cancer Res 66, 3126–3136.
Zamzami, N. and Kroemer, G. (2001). The mitochondrion in apoptosis: how Pandora’s box opens. Nat Rev Mol Cell Biol 2, 67–71.
Zhivotovsky, B., Hanson, K. P., and Orrenius, S. (1998a). Back to the future: the role of cytochrome c in cell death. Cell Death Differ 5, 459–460.
Zhivotovsky, B., Orrenius, S., Brustugun, O. T., and Doskeland, S. O. (1998b). Injected cytochrome c induces apoptosis. Nature 391, 449–450.
Zornig, M., Hueber, A., Baum, W., and Evan, G. (2001). Apoptosis regulators and their role in tumorigenesis. Biochim Biophys Acta 1551, F1–37.
Zou, H., Li, Y., Liu, X., and Wang, X. (1999). An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J Biol Chem 274, 11549–11556.
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Chalah, A., Khosravi-Far, R. (2008). The Mitochondrial Death Pathway. In: Programmed Cell Death in Cancer Progression and Therapy. Advances in Experimental Medicine and Biology, vol 615. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6554-5_3
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