J. Exp. Med., Volume 189, Number 2, January 18, 1999 381-394

Mitochondrial Release of Caspase-2 and -9 during the Apoptotic Process

By Santos A. Susin,^* Hans K. Lorenzo, Naoufal Zamzami,^* Isabel Marzo,^* Catherine Brenner,^*§ Nathanael Larochette,^* Marie-Christine Prévost, Pedro M. Alzari, and Guido Kroemer^*

From ^* Centre National de la Recherche Scientifique, UPR 420, F-94801 Villejuif, France;  Unité de Biochimie Structurale, Institut Pasteur, F-75724 Paris Cedex 15, France; ^§ Centre National de la Recherche Scientifique, UPRES-A6022, Université de Technologie de Compiègne, F-60200 Compiègne, France; and  Unité d'Oncologie Virale, Institut Pasteur, F-75724 Paris Cedex 15, France

The barrier function of mitochondrial membranes is perturbed early during the apoptotic process. Here we show that the mitochondria contain a caspase-like enzymatic activity cleaving the caspase substrate Z-VAD.afc, in addition to three biological activities previously suggested to participate in the apoptotic process: (a) cytochrome c; (b) an apoptosis-inducing factor (AIF) which causes isolated nuclei to undergo apoptosis in vitro; and (c) a DNAse activity. All of these factors, which are biochemically distinct, are released upon opening of the permeability transition (PT) pore in a coordinate, Bcl-2-inhibitable fashion. Caspase inhibitors fully neutralize the Z-VAD.afc-cleaving activity, have a limited effect on the AIF activity, and have no effect at all on the DNase activities. Purification of proteins reacting with the biotinylated caspase substrate Z-VAD, immunodetection, and immunodepletion experiments reveal the presence of procaspase-2 and -9 in mitochondria. Upon induction of PT pore opening, these procaspases are released from purified mitochondria and become activated. Similarly, upon induction of apoptosis, both procaspases redistribute from the mitochondrion to the cytosol and are processed to generate enzymatically active caspases. This redistribution is inhibited by Bcl-2. Recombinant caspase-2 and -9 suffice to provoke full-blown apoptosis upon microinjection into cells. Altogether, these data suggest that caspase-2 and -9 zymogens are essentially localized in mitochondria and that the disruption of the outer mitochondrial membrane occurring early during apoptosis may be critical for their subcellular redistribution and activation.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Balakrishnan, K., Wierda, W. G., Keating, M. J., Gandhi, V. (2008). Gossypol, a BH3 mimetic, induces apoptosis in chronic lymphocytic leukemia cells. Blood 112: 1971-1980 [Abstract] [Full Text]  
• Luo, J. Z., Luo, L. (2008). Ginseng on Hyperglycemia: Effects and Mechanisms. Evid Based Complement Alternat Med 0: nem178v1-nem178 [Abstract] [Full Text]  
• Ho, A. T., Li, Q. H., Okada, H., Mak, T. W., Zacksenhaus, E. (2007). XIAP Activity Dictates Apaf-1 Dependency for Caspase 9 Activation. Mol. Cell. Biol. 27: 5673-5685 [Abstract] [Full Text]  
• Baumgartner, H. K., Gerasimenko, J. V., Thorne, C., Ashurst, L. H., Barrow, S. L., Chvanov, M. A., Gillies, S., Criddle, D. N., Tepikin, A. V., Petersen, O. H., Sutton, R., Watson, A. J. M., Gerasimenko, O. V. (2007). Caspase-8-mediated apoptosis induced by oxidative stress is independent of the intrinsic pathway and dependent on cathepsins. Am. J. Physiol. Gastrointest. Liver Physiol. 293: G296-G307 [Abstract] [Full Text]  
• Adhihetty, P. J., Ljubicic, V., Hood, D. A. (2007). Effect of chronic contractile activity on SS and IMF mitochondrial apoptotic susceptibility in skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 292: E748-E755 [Abstract] [Full Text]  
• Murakami, Y., Aizu-Yokota, E., Sonoda, Y., Ohta, S., Kasahara, T. (2007). Suppression of Endoplasmic Reticulum Stress-induced Caspase Activation and Cell Death by the Overexpression of Bcl-xL or Bcl-2. J Biochem 141: 401-410 [Abstract] [Full Text]  
• Mhaidat, N. M., Wang, Y., Kiejda, K. A., Zhang, X. D., Hersey, P. (2007). Docetaxel-induced apoptosis in melanoma cells is dependent on activation of caspase-2. Molecular Cancer Therapeutics 6: 752-761 [Abstract] [Full Text]  
• Kroemer, G., Galluzzi, L., Brenner, C. (2007). Mitochondrial Membrane Permeabilization in Cell Death. Physiol. Rev. 87: 99-163 [Abstract] [Full Text]  
• Luo, J. Z., Luo, L. (2006). American Ginseng Stimulates Insulin Production and Prevents Apoptosis through Regulation of Uncoupling Protein-2 in Cultured {beta} Cells. Evid Based Complement Alternat Med 3: 365-372 [Abstract] [Full Text]  
• Peluffo, M. C, Bussmann, L., Stouffer, R. L, Tesone, M. (2006). Expression of caspase-2, -3, -8 and -9 proteins and enzyme activity in the corpus luteum of the rat at different stages during the natural estrous cycle.. Reproduction 132: 465-475 [Abstract] [Full Text]  
• Lee, T.-J., Kim, E. J., Kim, S., Jung, E. M., Park, J.-W., Jeong, S. H., Park, S. E., Yoo, Y. H., Kwon, T. K. (2006). Caspase-dependent and caspase-independent apoptosis induced by evodiamine in human leukemic U937 cells.. Molecular Cancer Therapeutics 5: 2398-2407 [Abstract] [Full Text]  
• Han, Y., Chen, Y.-S., Liu, Z., Bodyak, N., Rigor, D., Bisping, E., Pu, W. T., Kang, P. M. (2006). Overexpression of HAX-1 Protects Cardiac Myocytes From Apoptosis Through Caspase-9 Inhibition. Circ. Res. 99: 415-423 [Abstract] [Full Text]  
• Brown, D., Yu, B. D., Joza, N., Benit, P., Meneses, J., Firpo, M., Rustin, P., Penninger, J. M., Martin, G. R. (2006). Loss of Aif function causes cell death in the mouse embryo, but the temporal progression of patterning is normal. Proc. Natl. Acad. Sci. USA 103: 9918-9923 [Abstract] [Full Text]  
• Kovbasnjuk, O., Mourtazina, R., Baibakov, B., Wang, T., Elowsky, C., Choti, M. A., Kane, A., Donowitz, M. (2005). The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer. Proc. Natl. Acad. Sci. USA 102: 19087-19092 [Abstract] [Full Text]  
• Qin, J.-Z., Ziffra, J., Stennett, L., Bodner, B., Bonish, B. K., Chaturvedi, V., Bennett, F., Pollock, P. M., Trent, J. M., Hendrix, M. J.C., Rizzo, P., Miele, L., Nickoloff, B. J. (2005). Proteasome Inhibitors Trigger NOXA-Mediated Apoptosis in Melanoma and Myeloma Cells. Cancer Res. 65: 6282-6293 [Abstract] [Full Text]  
• Mader, J. S., Salsman, J., Conrad, D. M., Hoskin, D. W. (2005). Bovine lactoferricin selectively induces apoptosis in human leukemia and carcinoma cell lines. Molecular Cancer Therapeutics 4: 612-624 [Abstract] [Full Text]  
• Park, M.-T., Kim, M.-J., Kang, Y.-H., Choi, S.-Y., Lee, J.-H., Choi, J.-A, Kang, C.-M., Cho, C.-K., Kang, S., Bae, S., Lee, Y.-S., Chung, H. Y., Lee, S.-J. (2005). Phytosphingosine in combination with ionizing radiation enhances apoptotic cell death in radiation-resistant cancer cells through ROS-dependent and -independent AIF release. Blood 105: 1724-1733 [Abstract] [Full Text]  
• Cheung, E. C. C., Melanson-Drapeau, L., Cregan, S. P., Vanderluit, J. L., Ferguson, K. L., McIntosh, W. C., Park, D. S., Bennett, S. A. L., Slack, R. S. (2005). Apoptosis-Inducing Factor Is a Key Factor in Neuronal Cell Death Propagated by BAX-Dependent and BAX-Independent Mechanisms. J. Neurosci. 25: 1324-1334 [Abstract] [Full Text]  
• Kang, Y.-H., Yi, M.-J., Kim, M.-J., Park, M.-T., Bae, S., Kang, C.-M., Cho, C.-K., Park, I.-C., Park, M.-J., Rhee, C. H., Hong, S.-I., Chung, H. Y., Lee, Y.-S., Lee, S.-J. (2004). Caspase-Independent Cell Death by Arsenic Trioxide in Human Cervical Cancer Cells: Reactive Oxygen Species-Mediated Poly(ADP-ribose) Polymerase-1 Activation Signals Apoptosis-Inducing Factor Release from Mitochondria. Cancer Res. 64: 8960-8967 [Abstract] [Full Text]  
• Guseva, N. V., Taghiyev, A. F., Sturm, M. T., Rokhlin, O. W., Cohen, M. B. (2004). Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Mediated Activation of Mitochondria-Associated Nuclear Factor-{kappa}B in Prostatic Carcinoma Cell Lines. Mol Cancer Res 2: 574-584 [Abstract] [Full Text]  
• Sakai, T., Liu, L., Teng, X., Mukai-Sakai, R., Shimada, H., Kaji, R., Mitani, T., Matsumoto, M., Toida, K., Ishimura, K., Shishido, Y., Mak, T. W., Fukui, K. (2004). Nucling Recruits Apaf-1/Pro-caspase-9 Complex for the Induction of Stress-induced Apoptosis. J. Biol. Chem. 279: 41131-41140 [Abstract] [Full Text]  
• Zorov, D. B., Kobrinsky, E., Juhaszova, M., Sollott, S. J. (2004). Examining Intracellular Organelle Function Using Fluorescent Probes: From Animalcules to Quantum Dots. Circ. Res. 95: 239-252 [Abstract] [Full Text]  
• Chandra, D., Choy, G., Deng, X., Bhatia, B., Daniel, P., Tang, D. G. (2004). Association of Active Caspase 8 with the Mitochondrial Membrane during Apoptosis: Potential Roles in Cleaving BAP31 and Caspase 3 and Mediating Mitochondrion-Endoplasmic Reticulum Cross Talk in Etoposide-Induced Cell Death. Mol. Cell. Biol. 24: 6592-6607 [Abstract] [Full Text]  
• Chen, Y.-W., Hwang, K. C., Yen, C.-C., Lai, Y.-L. (2004). Fullerene derivatives protect against oxidative stress in RAW 264.7 cells and ischemia-reperfused lungs. Am. J. Physiol. Regul. Integr. Comp. Physiol. 287: R21-R26 [Abstract] [Full Text]  
• Kuo, C.-C., Hsieh, H.-P., Pan, W.-Y., Chen, C.-P., Liou, J.-P., Lee, S.-J., Chang, Y.-L., Chen, L.-T., Chen, C.-T., Chang, J.-Y. (2004). BPR0L075, a Novel Synthetic Indole Compound with Antimitotic Activity in Human Cancer Cells, Exerts Effective Antitumoral Activity in Vivo. Cancer Res. 64: 4621-4628 [Abstract] [Full Text]  
• Yamamoto, N., Jiang, P., Yang, M., Xu, M., Yamauchi, K., Tsuchiya, H., Tomita, K., Wahl, G. M., Moossa, A. R., Hoffman, R. M. (2004). Cellular Dynamics Visualized in Live Cells in Vitro and in Vivo by Differential Dual-Color Nuclear-Cytoplasmic Fluorescent-Protein Expression. Cancer Res. 64: 4251-4256 [Abstract] [Full Text]  
• Qin, Y., Vanden Hoek, T. L., Wojcik, K., Anderson, T., Li, C.-Q., Shao, Z.-H., Becker, L. B., Hamann, K. J. (2004). Caspase-dependent cytochrome c release and cell death in chick cardiomyocytes after simulated ischemia-reperfusion. Am. J. Physiol. Heart Circ. Physiol. 286: H2280-H2286 [Abstract] [Full Text]  
• Katoh, I., Tomimori, Y., Ikawa, Y., Kurata, S.-i. (2004). Dimerization and Processing of Procaspase-9 by Redox Stress in Mitochondria. J. Biol. Chem. 279: 15515-15523 [Abstract] [Full Text]  
• Zhang, X. D., Gillespie, S. K., Hersey, P. (2004). Staurosporine induces apoptosis of melanoma by both caspase-dependent and -independent apoptotic pathways. Molecular Cancer Therapeutics 3: 187-197 [Abstract] [Full Text]  
• Chen, H., Chung, S., Sukumar, S. (2004). HOXA5-Induced Apoptosis in Breast Cancer Cells Is Mediated by Caspases 2 and 8. Mol. Cell. Biol. 24: 924-935 [Abstract] [Full Text]  
• Abmayr, S., Crawford, R.W., Chamberlain, J.S. (2004). Characterization of ARC, apoptosis repressor interacting with CARD, in normal and dystrophin-deficient skeletal muscle. Hum Mol Genet 13: 213-221 [Abstract] [Full Text]  
• Waxman, D. J., Schwartz, P. S. (2003). Harnessing Apoptosis for Improved Anticancer Gene Therapy. Cancer Res. 63: 8563-8572 [Abstract] [Full Text]  
• Ruchalski, K., Mao, H., Singh, S. K., Wang, Y., Mosser, D. D., Li, F., Schwartz, J. H., Borkan, S. C. (2003). HSP72 inhibits apoptosis-inducing factor release in ATP-depleted renal epithelial cells. Am. J. Physiol. Cell Physiol. 285: C1483-C1493 [Abstract] [Full Text]  
• Thiantanawat, A., Long, B. J., Brodie, A. M. (2003). Signaling Pathways of Apoptosis Activated by Aromatase Inhibitors and Antiestrogens. Cancer Res. 63: 8037-8050 [Abstract] [Full Text]  
• Redlak, M. J., Dennis, M. S., Miller, T. A. (2003). Apoptosis is a major mechanism of deoxycholate-induced gastric mucosal cell death. Am. J. Physiol. Gastrointest. Liver Physiol. 285: G870-G879 [Abstract] [Full Text]  
• Colell, A., Garcia-Ruiz, C., Lluis, J. M., Coll, O., Mari, M., Fernandez-Checa, J. C. (2003). Cholesterol Impairs the Adenine Nucleotide Translocator-mediated Mitochondrial Permeability Transition through Altered Membrane Fluidity. J. Biol. Chem. 278: 33928-33935 [Abstract] [Full Text]  
• Chandra, D., Tang, D. G. (2003). Mitochondrially Localized Active Caspase-9 and Caspase-3 Result Mostly from Translocation from the Cytosol and Partly from Caspase-mediated Activation in the Organelle. LACK OF EVIDENCE FOR Apaf-1-MEDIATED PROCASPASE-9 ACTIVATION IN THE MITOCHONDRIA. J. Biol. Chem. 278: 17408-17420 [Abstract] [Full Text]  
• Korichneva, I., Waka, J., Hammerling, U. (2003). Regulation of the Cardiac Mitochondrial Membrane Potential by Retinoids. J. Pharmacol. Exp. Ther. 305: 426-433 [Abstract] [Full Text]  
• Grayson, J. M., Laniewski, N. G., Lanier, J. G., Ahmed, R. (2003). Mitochondrial Potential and Reactive Oxygen Intermediates in Antigen-Specific CD8+ T Cells During Viral Infection. J. Immunol. 170: 4745-4751 [Abstract] [Full Text]  
• Kinjo, T, Kamiyama, K, Chinen, K, Iwamasa, T, Kurihara, K, Hamada, T (2003). Squamous metaplasia induced by transfection of human papillomavirus DNA into cultured adenocarcinoma cells. Mol. Pathol. 56: 97-108 [Abstract] [Full Text]  
• Martinet, W., Knaapen, M. W.M., De Meyer, G. R.Y., Herman, A. G., Kockx, M. M. (2003). Overexpression of the Anti-Apoptotic Caspase-2 Short Isoform in Macrophage-Derived Foam Cells of Human Atherosclerotic Plaques. Am. J. Pathol. 162: 731-736 [Abstract] [Full Text]  
• Ricci, J.-E., Gottlieb, R. A., Green, D. R. (2003). Caspase-mediated loss of mitochondrial function and generation of reactive oxygen species during apoptosis. JCB 160: 65-75 [Abstract] [Full Text]  
• Maestre, I., Jordan, J., Calvo, S., Reig, J. A., Cena, V., Soria, B., Prentki, M., Roche, E. (2003). Mitochondrial Dysfunction Is Involved in Apoptosis Induced by Serum Withdrawal and Fatty Acids in the {beta}-Cell Line Ins-1. Endocrinology 144: 335-345 [Abstract] [Full Text]  
• Schwartz, P. S., Chen, C.-S., Waxman, D. J. (2002). Enhanced Bystander Cytotoxicity of P450 Gene-directed Enzyme Prodrug Therapy by Expression of the Antiapoptotic Factor p35. Cancer Res. 62: 6928-6937 [Abstract] [Full Text]  
• Yin, X.-M., Luo, Y., Cao, G., Bai, L., Pei, W., Kuharsky, D. K., Chen, J. (2002). Bid-mediated Mitochondrial Pathway Is Critical to Ischemic Neuronal Apoptosis and Focal Cerebral Ischemia. J. Biol. Chem. 277: 42074-42081 [Abstract] [Full Text]  
• Kominsky, D. J., Bickel, R. J., Tyler, K. L. (2002). Reovirus-Induced Apoptosis Requires Mitochondrial Release of Smac/DIABLO and Involves Reduction of Cellular Inhibitor of Apoptosis Protein Levels. J. Virol. 76: 11414-11424 [Abstract] [Full Text]  
• Garcia-Ruiz, C., Colell, A., Morales, A., Calvo, M., Enrich, C., Fernandez-Checa, J. C. (2002). Trafficking of Ganglioside GD3 to Mitochondria by Tumor Necrosis Factor-alpha. J. Biol. Chem. 277: 36443-36448 [Abstract] [Full Text]  
• Mendelsohn, A. R., Hamer, J. D., Wang, Z. B., Brent, R. (2002). Cyclin D3 activates Caspase 2, connecting cell proliferation with cell death. Proc. Natl. Acad. Sci. USA 99: 6871-6876 [Abstract] [Full Text]  
• Huo, J., Luo, R.-H., Metz, S. A., Li, G. (2002). Activation of Caspase-2 Mediates the Apoptosis Induced by GTP-Depletion in Insulin-Secreting (HIT-T15) Cells. Endocrinology 143: 1695-1704 [Abstract] [Full Text]  
• Paroni, G., Henderson, C., Schneider, C., Brancolini, C. (2002). Caspase-2 Can Trigger Cytochrome c Release and Apoptosis from the Nucleus. J. Biol. Chem. 277: 15147-15161 [Abstract] [Full Text]  
• Herold, M. J., Kuss, A. W., Kraus, C., Berberich, I. (2002). Mitochondria-Dependent Caspase-9 Activation Is Necessary for Antigen Receptor-Mediated Effector Caspase Activation and Apoptosis in WEHI 231 Lymphoma Cells. J. Immunol. 168: 3902-3909 [Abstract] [Full Text]  
• Guo, Y., Srinivasula, S. M., Druilhe, A., Fernandes-Alnemri, T., Alnemri, E. S. (2002). Caspase-2 Induces Apoptosis by Releasing Proapoptotic Proteins from Mitochondria. J. Biol. Chem. 277: 13430-13437 [Abstract] [Full Text]  
• Ogita, K., Okuda, H., Kitano, M., Fujinami, Y., Ozaki, K., Yoneda, Y. (2002). Localization of Activator Protein-1 Complex with DNA Binding Activity in Mitochondria of Murine Brain after In Vivo Treatment with Kainate. J. Neurosci. 22: 2561-2570 [Abstract] [Full Text]  
• Piccotti, L., Marchetti, C., Migliorati, G., Roberti, R., Corazzi, L. (2002). Exogenous Phospholipids Specifically Affect Transmembrane Potential of Brain Mitochondria and Cytochrome c Release. J. Biol. Chem. 277: 12075-12081 [Abstract] [Full Text]  
• Risso, A., Braidot, E., Sordano, M. C., Vianello, A., Macri, F., Skerlavaj, B., Zanetti, M., Gennaro, R., Bernardi, P. (2002). BMAP-28, an Antibiotic Peptide of Innate Immunity, Induces Cell Death through Opening of the Mitochondrial Permeability Transition Pore. Mol. Cell. Biol. 22: 1926-1935 [Abstract] [Full Text]  
• Bruno, S., Tenca, C., Saverino, D., Ciccone, E., Grossi, C. E. (2002). Apoptosis of squamous cells at different stages of carcinogenesis following 4-HPR treatment. Carcinogenesis 23: 447-456 [Abstract] [Full Text]  
• Nakamura, Y., Kawakami, M., Yoshihiro, A., Miyoshi, N., Ohigashi, H., Kawai, K., Osawa, T., Uchida, K. (2002). Involvement of the Mitochondrial Death Pathway in Chemopreventive Benzyl Isothiocyanate-induced Apoptosis. J. Biol. Chem. 277: 8492-8499 [Abstract] [Full Text]  
• Madesh, M., Antonsson, B., Srinivasula, S. M., Alnemri, E. S., Hajnoczky, G. (2002). Rapid Kinetics of tBid-induced Cytochrome c and Smac/DIABLO Release and Mitochondrial Depolarization. J. Biol. Chem. 277: 5651-5659 [Abstract] [Full Text]  
• Paul, C., Manero, F., Gonin, S., Kretz-Remy, C., Virot, S., Arrigo, A.-P. (2002). Hsp27 as a Negative Regulator of Cytochrome c Release. Mol. Cell. Biol. 22: 816-834 [Abstract] [Full Text]  
• Stegh, A. H., Barnhart, B. C., Volkland, J., Algeciras-Schimnich, A., Ke, N., Reed, J. C., Peter, M. E. (2002). Inactivation of Caspase-8 on Mitochondria of Bcl-xL-expressing MCF7-Fas Cells. ROLE FOR THE BIFUNCTIONAL APOPTOSIS REGULATOR PROTEIN. J. Biol. Chem. 277: 4351-4360 [Abstract] [Full Text]  
• Madesh, M., Hajnoczky, G. (2001). VDAC-dependent permeabilization of the outer mitochondrial membrane by superoxide induces rapid and massive cytochrome c release. JCB 155: 1003-1016 [Abstract] [Full Text]  
• Almeida, A., Almeida, J., Bolanos, J. P., Moncada, S. (2001). Different responses of astrocytes and neurons to nitric oxide: The role of glycolytically generated ATP in astrocyte protection. Proc. Natl. Acad. Sci. USA 10.1073/pnas.261560998v1 [Abstract] [Full Text]  
• Schwartz, P. S., Waxman, D. J. (2001). Cyclophosphamide Induces Caspase 9-Dependent Apoptosis in 9L Tumor Cells. Mol. Pharmacol. 60: 1268-1279 [Abstract] [Full Text]  
• Secchiero, P., Gonelli, A., Celeghini, C., Mirandola, P., Guidotti, L., Visani, G., Capitani, S., Zauli, G. (2001). Activation of the nitric oxide synthase pathway represents a key component of tumor necrosis factor-related apoptosis-inducing ligand-mediated cytotoxicity on hematologic malignancies. Blood 98: 2220-2228 [Abstract] [Full Text]  
• Chen, W., Jin, W., Tian, H., Sicurello, P., Frank, M., Orenstein, J. M., Wahl, S. M. (2001). Requirement for Transforming Growth Factor {beta}1 in Controlling T Cell Apoptosis. JEM 194: 439-454 [Abstract] [Full Text]  
• Phenix, B. N., Lum, J. J., Nie, Z., Sanchez-Dardon, J., Badley, A. D. (2001). Antiapoptotic mechanism of HIV protease inhibitors: preventing mitochondrial transmembrane potential loss. Blood 98: 1078-1085 [Abstract] [Full Text]  
• Troy, C. M., Rabacchi, S. A., Hohl, J. B., Angelastro, J. M., Greene, L. A., Shelanski, M. L. (2001). Death in the Balance: Alternative Participation of the Caspase-2 and -9 Pathways in Neuronal Death Induced by Nerve Growth Factor Deprivation. J. Neurosci. 21: 5007-5016 [Abstract] [Full Text]  
• Liu, H., Perlman, H., Pagliari, L. J., Pope, R. M. (2001). Constitutively Activated Akt-1 Is Vital for the Survival of Human Monocyte-differentiated Macrophages: Role of Mcl-1, Independent of Nuclear Factor (NF)-{kappa}B, Bad, or Caspase Activation. JEM 194: 113-126 [Abstract] [Full Text]  
• Motoori, S., Majima, H. J., Ebara, M., Kato, H., Hirai, F., Kakinuma, S., Yamaguchi, C., Ozawa, T., Nagano, T., Tsujii, H., Saisho, H. (2001). Overexpression of Mitochondrial Manganese Superoxide Dismutase Protects against Radiation-induced Cell Death in the Human Hepatocellular Carcinoma Cell Line HLE. Cancer Res. 61: 5382-5388 [Abstract] [Full Text]  
• Hu, X., Christian, P. J., Thompson, K. E., Glenn Sipes, I., Hoyer, P. B. (2001). Apoptosis Induced in Rats by 4-Vinylcyclohexene Diepoxide Is Associated with Activation of the Caspase Cascades. Biol. Reprod. 65: 87-93 [Abstract] [Full Text]  
• Condorelli, F., Salomoni, P., Cotteret, S., Cesi, V., Srinivasula, S. M., Alnemri, E. S., Calabretta, B. (2001). Caspase Cleavage Enhances the Apoptosis-Inducing Effects of BAD. Mol. Cell. Biol. 21: 3025-3036 [Abstract] [Full Text]  
• Sciacco, M., Fagiolari, G., Lamperti, C., Messina, S., Bazzi, P., Napoli, L., Chiveri, L., Prelle, A., Comi, G.P., Bresolin, N., Scarlato, G., Moggio, M. (2001). Lack of apoptosis in mitochondrial encephalomyopathies. Neurology 56: 1070-1074 [Abstract] [Full Text]  
• Hisatomi, T., Sakamoto, T., Murata, T., Yamanaka, I., Oshima, Y., Hata, Y., Ishibashi, T., Inomata, H., Susin, S. A., Kroemer, G. (2001). Relocalization of Apoptosis-Inducing Factor in Photoreceptor Apoptosis Induced by Retinal Detachment in Vivo. Am. J. Pathol. 158: 1271-1278 [Abstract] [Full Text]  
• Northington, F. J., Ferriero, D. M., Flock, D. L., Martin, L. J. (2001). Delayed Neurodegeneration in Neonatal Rat Thalamus after Hypoxia-Ischemia Is Apoptosis. J. Neurosci. 21: 1931-1938 [Abstract] [Full Text]  
• Kirkland, R. A., Franklin, J. L. (2001). Evidence for Redox Regulation of Cytochrome c Release during Programmed Neuronal Death: Antioxidant Effects of Protein Synthesis and Caspase Inhibition. J. Neurosci. 21: 1949-1963 [Abstract] [Full Text]  
• Dispersyn, G. D., Borgers, M. (2001). Apoptosis in the Heart: About Programmed Cell Death and Survival. Physiology 16: 41-47 [Abstract] [Full Text]  
• Zermati, Y., Garrido, C., Amsellem, S., Fishelson, S., Bouscary, D., Valensi, F., Varet, B., Solary, E., Hermine, O. (2001). Caspase Activation Is Required for Terminal Erythroid Differentiation. JEM 193: 247-254 [Abstract] [Full Text]  
• Salvucci, O., Carsana, M., Bersani, I., Tragni, G., Anichini, A. (2001). Antiapoptotic Role of Endogenous Nitric Oxide in Human Melanoma Cells. Cancer Res. 61: 318-326 [Abstract] [Full Text]  
• Chang, H. Y., Yang, X. (2000). Proteases for Cell Suicide: Functions and Regulation of Caspases. Microbiol. Mol. Biol. Rev. 64: 821-846 [Abstract] [Full Text]  
• Droin, N., Beauchemin, M., Solary, E., Bertrand, R. (2000). Identification of a Caspase-2 Isoform that Behaves as an Endogenous Inhibitor of the Caspase Cascade. Cancer Res. 60: 7039-7047 [Abstract] [Full Text]  
• Hajnoczky, G., Csordas, G., Madesh, M., Pacher, P. (2000). The machinery of local Ca2+ signalling between sarco-endoplasmic reticulum and mitochondria. J. Physiol. 529: 69-81 [Abstract] [Full Text]  
• Thomas, W. D., Zhang, X. D., Franco, A. V., Nguyen, T., Hersey, P. (2000). TNF-Related Apoptosis-Inducing Ligand-Induced Apoptosis of Melanoma Is Associated with Changes in Mitochondrial Membrane Potential and Perinuclear Clustering of Mitochondria. J. Immunol. 165: 5612-5620 [Abstract] [Full Text]  
• Özören, N., Kim, K., Burns, T. F., Dicker, D. T., Moscioni, A. D., El-Deiry, W. S. (2000). The Caspase 9 Inhibitor Z-LEHD-FMK Protects Human Liver Cells while Permitting Death of Cancer Cells Exposed to Tumor Necrosis Factor-related Apoptosis-inducing Ligand. Cancer Res. 60: 6259-6265 [Abstract] [Full Text]  
• 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. (2000). Apoptosis Control in Syncytia Induced by the HIV Type 1-Envelope Glycoprotein Complex: Role of Mitochondria and Caspases. JEM 192: 1081-1092 [Abstract] [Full Text]  
• RIPPO, M. R., MALISAN, F., RAVAGNAN, L., TOMASSINI, B., CONDO, I., COSTANTINI, P., SUSIN, S. A., RUFINI, A., TODARO, M., KROEMER, G., TESTI, R. (2000). GD3 ganglioside directly targets mitochondria in a bcl-2-controlled fashion. FASEB J. 14: 2047-2054 [Abstract] [Full Text]  
• Hennino, A., Berard, M., Casamayor-Palleja, M., Krammer, P. H., Defrance, T. (2000). Regulation of the Fas Death Pathway by FLICE-Inhibitory Protein in Primary Human B Cells. J. Immunol. 165: 3023-3030 [Abstract] [Full Text]  
• von Ahsen, O., Renken, C., Perkins, G., Kluck, R. M., Bossy-Wetzel, E., Newmeyer, D. D. (2000). Preservation of Mitochondrial Structure and Function after Bid- or Bax-mediated Cytochrome c Release. JCB 150: 1027-1036 [Abstract] [Full Text]  
• Watabe, M., Machida, K., Osada, H. (2000). MT-21 Is a Synthetic Apoptosis Inducer That Directly Induces Cytochrome c Release from Mitochondria. Cancer Res. 60: 5214-5222 [Abstract] [Full Text]  
• Torban, E., Eccles, M. R., Favor, J., Goodyer, P. R. (2000). PAX2 Suppresses Apoptosis in Renal Collecting Duct Cells. Am. J. Pathol. 157: 833-842 [Abstract] [Full Text]  
• 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. (2000). Two Distinct Pathways Leading to Nuclear Apoptosis. JEM 192: 571-580 [Abstract] [Full Text]  
• Li, M., Beg, A. A. (2000). Induction of Necrotic-Like Cell Death by Tumor Necrosis Factor Alpha and Caspase Inhibitors: Novel Mechanism for Killing Virus-Infected Cells. J. Virol. 74: 7470-7477 [Abstract] [Full Text]  
• Danen-van Oorschot, A. A. A. M., van der Eb, A. J., Noteborn, M. H. M. (2000). The Chicken Anemia Virus-Derived Protein Apoptin Requires Activation of Caspases for Induction of Apoptosis in Human Tumor Cells. J. Virol. 74: 7072-7078 [Abstract] [Full Text]  
• Stegh, A. H., Herrmann, H., Lampel, S., Weisenberger, D., Andrä, K., Seper, M., Wiche, G., Krammer, P. H., Peter, M. E. (2000). Identification of the Cytolinker Plectin as a Major Early In Vivo Substrate for Caspase 8 during CD95- and Tumor Necrosis Factor Receptor-Mediated Apoptosis. Mol. Cell. Biol. 20: 5665-5679 [Abstract] [Full Text]  
• Kluza, J., Lansiaux, A., Wattez, N., Mahieu, C., Osheroff, N., Bailly, C. (2000). Apoptotic Response of HL-60 Human Leukemia Cells to the Antitumor Drug TAS-103. Cancer Res. 60: 4077-4084 [Abstract] [Full Text]  
• Schlottmann, K., Wachs, F.-P., Christian Krieg, R., Kullmann, F., Schölmerich, J., Rogler, G. (2000). Characterization of Bile Salt-induced Apoptosis in Colon Cancer Cell Lines. Cancer Res. 60: 4270-4276 [Abstract] [Full Text]  
• Blanc, C., Deveraux, Q. L., Krajewski, S., Jänicke, R. U., Porter, A. G., Reed, J. C., Jaggi, R., Marti, A. (2000). Caspase-3 Is Essential for Procaspase-9 Processing and Cisplatin-induced Apoptosis of MCF-7 Breast Cancer Cells. Cancer Res. 60: 4386-4390 [Abstract] [Full Text]  
• Dumont, C., Durrbach, A., Bidere, N., Rouleau, M., Kroemer, G., Bernard, G., Hirsch, F., Charpentier, B., Susin, S. A., Senik, A. (2000). Caspase-independent commitment phase to apoptosis in activated blood T lymphocytes: reversibility at low apoptotic insult. Blood 96: 1030-1038 [Abstract] [Full Text]  
• Costantini, P., Jacotot, E., Decaudin, D., Kroemer, G. (2000). Mitochondrion as a Novel Target of Anticancer Chemotherapy. JNCI J Natl Cancer Inst 92: 1042-1053 [Abstract] [Full Text]  
• Barry, M., Heibein, J. A., Pinkoski, M. J., Lee, S.-F., Moyer, R. W., Green, D. R., Bleackley, R. C. (2000). 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: 3781-3794 [Abstract] [Full Text]  
• Walczak, H., Bouchon, A., Stahl, H., Krammer, P. H. (2000). Tumor Necrosis Factor-related Apoptosis-inducing Ligand Retains Its Apoptosis-inducing Capacity on Bcl-2- or Bcl-xL-overexpressing Chemotherapy-resistant Tumor Cells. Cancer Res. 60: 3051-3057 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS