J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/07/25/13 $2.00
Volume 186, Number 1, July 7, 1997 25-37

The Central Executioner of Apoptosis: Multiple Connections between Protease Activation and Mitochondria in Fas/APO-1/CD95- and Ceramide-induced Apoptosis

By Santos A. Susin,^* Naoufal Zamzami,^* Maria Castedo,^* Eric Daugas,^* Hong-Gang Wang, Stephan Geley,^§ Florence Fassy, John C. Reed, and Guido Kroemer^*

From the ^* Centre National de la Recherche Scientifique-UPR420, B.P.8, F-94801 Villejuif, France;  The Burnham Institute, La Jolla, California 92037; ^§ Institute for General and Experimental Pathology of the University of Innsbruck, A-6020 Innsbruck, Austria; and  Division Santé, Domain Immunologie, ROUSSEL UCLAF, F-93235 Romainville, France

According to current understanding, cytoplasmic events including activation of protease cascades and mitochondrial permeability transition (PT) participate in the control of nuclear apoptosis. However, the relationship between protease activation and PT has remained elusive. When apoptosis is induced by cross-linking of the Fas/APO-1/CD95 receptor, activation of interleukin-1 converting enzyme (ICE; caspase 1) or ICE-like enzymes precedes the disruption of the mitochondrial inner transmembrane potential (_m). In contrast, cytosolic CPP32/ Yama/Apopain/caspase 3 activation, plasma membrane phosphatidyl serine exposure, and nuclear apoptosis only occur in cells in which the _m is fully disrupted. Transfection with the cowpox protease inhibitor crmA or culture in the presence of the synthetic ICE-specific inhibitor Ac-YVAD.cmk both prevent the _m collapse and subsequent apoptosis. Cytosols from anti-Fas-treated human lymphoma cells accumulate an activity that induces PT in isolated mitochondria in vitro and that is neutralized by crmA or Ac-YVAD.cmk. Recombinant purified ICE suffices to cause isolated mitochondria to undergo PT-like large amplitude swelling and to disrupt their _m. In addition, ICE-treated mitochondria release an apoptosis-inducing factor (AIF) that induces apoptotic changes (chromatin condensation and oligonucleosomal DNA fragmentation) in isolated nuclei in vitro. AIF is a protease (or protease activator) that can be inhibited by the broad spectrum apoptosis inhibitor Z-VAD.fmk and that causes the proteolytical activation of CPP32. Although Bcl-2 is a highly efficient inhibitor of mitochondrial alterations (large amplitude swelling + _m collapse + release of AIF) induced by prooxidants or cytosols from ceramide-treated cells, it has no effect on the ICE-induced mitochondrial PT and AIF release. These data connect a protease activation pathway with the mitochondrial phase of apoptosis regulation. In addition, they provide a plausible explanation of why Bcl-2 fails to interfere with Fas-triggered apoptosis in most cell types, yet prevents ceramide- and prooxidant-induced apoptosis.

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• Okada, S., Li, Q., Whitin, J. C., Clayberger, C., Krensky, A. M. (2003). Intracellular Mediators of Granulysin-Induced Cell Death. J. Immunol. 171: 2556-2562 [Abstract] [Full Text]  
• Pastorino, J. G., Shulga, N., Hoek, J. B. (2003). TNF-{alpha}-induced cell death in ethanol-exposed cells depends on p38 MAPK signaling but is independent of Bid and caspase-8. Am. J. Physiol. Gastrointest. Liver Physiol. 285: G503-G516 [Abstract] [Full Text]  
• Blom, W. M., de Bont, H. J. G. M., Nagelkerke, J. F. (2003). Regional Loss of the Mitochondrial Membrane Potential in the Hepatocyte Is Rapidly Followed by Externalization of Phosphatidylserines at That Specific Site during Apoptosis. J. Biol. Chem. 278: 12467-12474 [Abstract] [Full Text]  
• Cande, C., Cecconi, F., Dessen, P., Kroemer, G. (2003). Apoptosis-inducing factor (AIF): key to the conserved caspase-independent pathways of cell death?. J. Cell Sci. 115: 4727-4734 [Abstract] [Full Text]  
• Ferraro-Peyret, C., Quemeneur, L., Flacher, M., Revillard, J.-P., Genestier, L. (2002). Caspase-Independent Phosphatidylserine Exposure During Apoptosis of Primary T Lymphocytes. J. Immunol. 169: 4805-4810 [Abstract] [Full Text]  
• Duan, L., Gan, H., Golan, D. E., Remold, H. G. (2002). Critical Role of Mitochondrial Damage in Determining Outcome of Macrophage Infection with Mycobacterium tuberculosis. J. Immunol. 169: 5181-5187 [Abstract] [Full Text]  
• Siskind, L. J., Kolesnick, R. N., Colombini, M. (2002). Ceramide Channels Increase the Permeability of the Mitochondrial Outer Membrane to Small Proteins. J. Biol. Chem. 277: 26796-26803 [Abstract] [Full Text]  
• Gergely, P. Jr., Niland, B., Gonchoroff, N., Pullmann, R. Jr., Phillips, P. E., Perl, A. (2002). Persistent Mitochondrial Hyperpolarization, Increased Reactive Oxygen Intermediate Production, and Cytoplasmic Alkalinization Characterize Altered IL-10 Signaling in Patients with Systemic Lupus Erythematosus. J. Immunol. 169: 1092-1101 [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]  
• Jacobson, J., Duchen, M. R. (2002). Mitochondrial oxidative stress and cell death in astrocytes -- requirement for stored Ca2+ and sustained opening of the permeability transition pore. J. Cell Sci. 115: 1175-1188 [Abstract] [Full Text]  
• Ma, J., Reed, K. A., Gallo, J. M. (2002). Cells Designed to Deliver Anticancer Drugs by Apoptosis. Cancer Res. 62: 1382-1387 [Abstract] [Full Text]  
• Decaudin, D., Castedo, M., Nemati, F., Beurdeley-Thomas, A., De Pinieux, G., Caron, A., Pouillart, P., Wijdenes, J., Rouillard, D., Kroemer, G., Poupon, M.-F. (2002). Peripheral Benzodiazepine Receptor Ligands Reverse Apoptosis Resistance of Cancer Cells in Vitro and in Vivo. Cancer Res. 62: 1388-1393 [Abstract] [Full Text]  
• Boehrer, S., Chow, K. U., Beske, F., Kukoc-Zivojnov, N., Puccetti, E., Ruthardt, M., Baum, C., Rangnekar, V. M., Hoelzer, D., Mitrou, P. S., Weidmann, E. (2002). In Lymphatic Cells Par-4 Sensitizes to Apoptosis by Down-Regulating Bcl-2 and Promoting Disruption of Mitochondrial Membrane Potential and Caspase Activation. Cancer Res. 62: 1768-1775 [Abstract] [Full Text]  
• Watts, G. S., Futscher, B. W., Isett, R., Gleason-Guzman, M., Kunkel, M. W., Salmon, S. E. (2001). cDNA Microarray Analysis of Multidrug Resistance: Doxorubicin Selection Produces Multiple Defects in Apoptosis Signaling Pathways. J. Pharmacol. Exp. Ther. 299: 434-441 [Abstract] [Full Text]  
• Herr, I., Debatin, K.-M. (2001). Cellular stress response and apoptosis in cancer therapy. Blood 98: 2603-2614 [Abstract] [Full Text]  
• Cuvillier, O., Levade, T. (2001). Sphingosine 1-phosphate antagonizes apoptosis of human leukemia cells by inhibiting release of cytochrome c and Smac/DIABLO from mitochondria. Blood 98: 2828-2836 [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]  
• Buckman, J. F., Reynolds, I. J. (2001). Spontaneous Changes in Mitochondrial Membrane Potential in Cultured Neurons. J. Neurosci. 21: 5054-5065 [Abstract] [Full Text]  
• Kaspar, A. A., Okada, S., Kumar, J., Poulain, F. R., Drouvalakis, K. A., Kelekar, A., Hanson, D. A., Kluck, R. M., Hitoshi, Y., Johnson, D. E., Froelich, C. J., Thompson, C. B., Newmeyer, D. D., Anel, A., Clayberger, C., Krensky, A. M. (2001). A Distinct Pathway of Cell-Mediated Apoptosis Initiated by Granulysin. J. Immunol. 167: 350-356 [Abstract] [Full Text]  
• Duan, L., Gan, H., Arm, J., Remold, H. G. (2001). Cytosolic Phospholipase A2 Participates with TNF-{{alpha}} in the Induction of Apoptosis of Human Macrophages Infected with Mycobacterium tuberculosis H37Ra. J. Immunol. 166: 7469-7476 [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]  
• LOEFFLER, M., DAUGAS, E., SUSIN, S. A., ZAMZAMI, N., METIVIER, D., NIEMINEN, A.-L., BROTHERS, G., PENNINGER, J. M., KROEMER, G. (2001). Dominant cell death induction by extramitochondrially targeted apoptosis-inducing factor. FASEB J. 15: 758-767 [Abstract] [Full Text]  
• JAFFREZOU, J.-P., BRUNO, A. P., MOISAND, A., LEVADE, T., LAURENT, G. (2001). Activation of a nuclear sphingomyelinase in radiation-induced apoptosis. FASEB J. 15: 123-133 [Abstract] [Full Text]  
• Matsumura, H., Shimizu, Y., Ohsawa, Y., Kawahara, A., Uchiyama, Y., Nagata, S. (2000). Necrotic Death Pathway in Fas Receptor Signaling. JCB 151: 1247-1256 [Abstract] [Full Text]  
• Gastman, B. R., Yin, X.-M., Johnson, D. E., Wieckowski, E., Wang, G.-Q., Watkins, S. C., Rabinowich, H. (2000). Tumor-induced Apoptosis of T Cells: Amplification by a Mitochondrial Cascade. Cancer Res. 60: 6811-6817 [Abstract] [Full Text]  
• Embade, N., Valerón, P. F., Aznar, S., López-Collazo, E., Lacal, J. C. (2000). Apoptosis Induced by Rac GTPase Correlates with Induction of FasL and Ceramides Production. Mol. Biol. Cell 11: 4347-4358 [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]  
• Li, S.-H., Lam, S., Cheng, A. L., Li, X.-J. (2000). Intranuclear huntingtin increases the expression of caspase-1 and induces apoptosis. Hum Mol Genet 9: 2859-2867 [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]  
• Ng, S. S. W., Tsao, M.-S., Chow, S., Hedley, D. W. (2000). Inhibition of Phosphatidylinositide 3-Kinase Enhances Gemcitabine-induced Apoptosis in Human Pancreatic Cancer Cells. Cancer Res. 60: 5451-5455 [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]  
• Nagahara, Y., Ikekita, M., Shinomiya, T. (2000). Immunosuppressant FTY720 Induces Apoptosis by Direct Induction of Permeability Transition and Release of Cytochrome c from Mitochondria. J. Immunol. 165: 3250-3259 [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]  
• 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]  
• Yu, R., Mandlekar, S., Kong, A.-N. T. (2000). Molecular Mechanisms of Butylated Hydroxylanisole-Induced Toxicity: Induction of Apoptosis through Direct Release of Cytochrome c. Mol. Pharmacol. 58: 431-437 [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]  
• PUSKAS, F., GERGELY, P. JR, BANKI, K., PERL, A. (2000). Stimulation of the pentose phosphate pathway and glutathione levels by dehydroascorbate, the oxidized form of vitamin C. FASEB J. 14: 1352-1361 [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]  
• Hatano, E., Bradham, C. A., Stark, A., Iimuro, Y., Lemasters, J. J., Brenner, D. A. (2000). The Mitochondrial Permeability Transition Augments Fas-induced Apoptosis in Mouse Hepatocytes. J. Biol. Chem. 275: 11814-11823 [Abstract] [Full Text]  
• Galan, A., Garcia-Bermejo, M. L., Troyano, A., Vilaboa, N. E., de Blas, E., Kazanietz, M. G., Aller, P. (2000). Stimulation of p38 Mitogen-activated Protein Kinase Is an Early Regulatory Event for the Cadmium-induced Apoptosis in Human Promonocytic Cells. J. Biol. Chem. 275: 11418-11424 [Abstract] [Full Text]  
• Chmura, S. J., Nodzenski, E., Kharbanda, S., Pandey, P., Quintans, J., Kufe, D. W., Weichselbaum, R. R. (2000). Down-Regulation of Ceramide Production Abrogates Ionizing Radiation-Induced Cytochrome c Release and Apoptosis. Mol. Pharmacol. 57: 792-796 [Abstract] [Full Text]  
• Grullich, C., Sullards, M. C., Fuks, Z., Merrill, A. H. Jr., Kolesnick, R. (2000). CD95(Fas/APO-1) Signals Ceramide Generation Independent of the Effector Stage of Apoptosis. J. Biol. Chem. 275: 8650-8656 [Abstract] [Full Text]  
• Gastman, B. R., Johnson, D. E., Whiteside, T. L., Rabinowich, H. (2000). Tumor-induced apoptosis of T lymphocytes: elucidation of intracellular apoptotic events. Blood 95: 2015-2023 [Abstract] [Full Text]  
• van Heerde, W. L, Robert-Offerman, S., Dumont, E., Hofstra, L., Doevendans, P. A, Smits, J. F.M, Daemen, M. J.A.P, Reutelingsperger, C. P.M (2000). Markers of apoptosis in cardiovascular tissues: focus on Annexin V. Cardiovasc Res 45: 549-559 [Abstract] [Full Text]  
• Harvey, K. J., Lukovic, D., Ucker, D. S. (2000). Caspase-dependent Cdk Activity Is a Requisite Effector of Apoptotic Death Events. JCB 148: 59-72 [Abstract] [Full Text]  
• Jacotot, E., Ravagnan, L., Loeffler, M., Ferri, K. F., Vieira, H. L.A., Zamzami, N., Costantini, P., Druillennec, S., Hoebeke, J., Briand, J. P., Irinopoulou, T., Daugas, E., Susin, S. A., Cointe, D., Xie, Z. H., Reed, J. C., Roques, B. P., Kroemer, G. (2000). The HIV-1 Viral Protein R Induces Apoptosis via a Direct Effect on the Mitochondrial Permeability Transition Pore. JEM 191: 33-46 [Abstract] [Full Text]  
• Nicholls, D. G., Budd, S. L. (2000). Mitochondria and Neuronal Survival. Physiol. Rev. 80: 315-360 [Abstract] [Full Text]  
• 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. (1999). The Pro-apoptotic Proteins, Bid and Bax, Cause a Limited Permeabilization of the Mitochondrial Outer Membrane that Is Enhanced by Cytosol. JCB 147: 809-822 [Abstract] [Full Text]  
• Kawabata, Y., Hirokawa, M., Kitabayashi, A., Horiuchi, T., Kuroki, J., Miura, A. B. (1999). Defective Apoptotic Signal Transduction Pathway Downstream of Caspase-3 in Human B-Lymphoma Cells: A Novel Mechanism of Nuclear Apoptosis Resistance. Blood 94: 3523-3530 [Abstract] [Full Text]  
• Reed, J. C. (1999). Dysregulation of Apoptosis in Cancer. JCO 17: 2941-2941 [Abstract] [Full Text]  
• Wang, C.-Y., Guttridge, D. C., Mayo, M. W., Baldwin, A. S. Jr. (1999). NF-kappa B Induces Expression of the Bcl-2 Homologue A1/Bfl-1 To Preferentially Suppress Chemotherapy-Induced Apoptosis. Mol. Cell. Biol. 19: 5923-5929 [Abstract] [Full Text]  
• Joshi, B., Li, L., Taffe, B. G., Zhu, Z., Wahl, S., Tian, H., Ben-Josef, E., Taylor, J. D., Porter, A. T., Tang, D. G. (1999). Apoptosis Induction by a Novel Anti-Prostate Cancer Compound, BMD188 (a Fatty Acid-containing Hydroxamic Acid), Requires the Mitochondrial Respiratory Chain. Cancer Res. 59: 4343-4355 [Abstract] [Full Text]  
• Filipovic, D. M., Meng, X., Reeves, W. B. (1999). Inhibition of PARP prevents oxidant-induced necrosis but not apoptosis in LLC-PK1 cells. Am. J. Physiol. Renal Physiol. 277: F428-F436 [Abstract] [Full Text]  
• Kristal, B. S., Brown, A. M. (1999). Apoptogenic Ganglioside GD3 Directly Induces the Mitochondrial Permeability Transition. J. Biol. Chem. 274: 23169-23175 [Abstract] [Full Text]  
• Scorrano, L., Petronilli, V., Di Lisa, F., Bernardi, P. (1999). Commitment to Apoptosis by GD3 Ganglioside Depends on Opening of the Mitochondrial Permeability Transition Pore. J. Biol. Chem. 274: 22581-22585 [Abstract] [Full Text]  
• Srivastava, R. K., Sollott, S. J., Khan, L., Hansford, R., Lakatta, E. G., Longo, D. L. (1999). Bcl-2 and Bcl-XL Block Thapsigargin-Induced Nitric Oxide Generation, c-Jun NH2-Terminal Kinase Activity, and Apoptosis. Mol. Cell. Biol. 19: 5659-5674 [Abstract] [Full Text]  
• Rosie Xing, , Kolesnick, R. (1999). Stress signaling of apoptosis via ceramide and c-jun kinase. Innate Immunity 5: 216-221 [Abstract]  
• Stefanis, L., Park, D. S., Friedman, W. J., Greene, L. A. (1999). Caspase-Dependent and -Independent Death of Camptothecin-Treated Embryonic Cortical Neurons. J. Neurosci. 19: 6235-6247 [Abstract] [Full Text]  
• Martinez-Lorenzo, M. J., Anel, A., Gamen, S., Monleon, I., Lasierra, P., Larrad, L., Pineiro, A., Alava, M. A., Naval, J. (1999). Activated Human T Cells Release Bioactive Fas Ligand and APO2 Ligand in Microvesicles. J. Immunol. 163: 1274-1281 [Abstract] [Full Text]  
• Maurer, B. J., Metelitsa, L. S., Seeger, R. C., Cabot, M. C., Reynolds, C. P. (1999). Increase of Ceramide and Induction of Mixed Apoptosis/Necrosis by N-(4-Hydroxyphenyl)- retinamide in Neuroblastoma Cell Lines. JNCI J Natl Cancer Inst 91: 1138-1146 [Abstract] [Full Text]  
• Pervaiz, S., Seyed, M. A., Hirpara, J. L., Clement, M.-V., Loh, K. W. (1999). Purified Photoproducts of Merocyanine 540 Trigger Cytochrome C Release and Caspase 8-Dependent Apoptosis in Human Leukemia and Melanoma Cells. Blood 93: 4096-4108 [Abstract] [Full Text]  
• Li, J., Bombeck, C. A., Yang, S., Kim, Y.-M., Billiar, T. R. (1999). Nitric Oxide Suppresses Apoptosis via Interrupting Caspase Activation and Mitochondrial Dysfunction in Cultured Hepatocytes. J. Biol. Chem. 274: 17325-17333 [Abstract] [Full Text]  
• Kroemer, G., de The, H. (1999). Arsenic Trioxide, a Novel Mitochondriotoxic Anticancer Agent?. JNCI J Natl Cancer Inst 91: 743-745 [Full Text]  
• Linsinger, G., Wilhelm, S., Wagner, H., Hacker, G. (1999). Uncouplers of Oxidative Phosphorylation Can Enhance a Fas Death Signal. Mol. Cell. Biol. 19: 3299-3311 [Abstract] [Full Text]  
• BRÁS, A., RUIZ-VELA, A., GONZÁLEZ DE BUITRAGO, G., MARTÍNEZ-A, C. (1999). Caspase activation by BCR cross-linking in immature B cells: differential effects on growth arrest and apoptosis. FASEB J. 13: 931-944 [Abstract] [Full Text]  
• Eguchi, Y., Srinivasan, A., Tomaselli, K. J., Shimizu, S., Tsujimoto, Y. (1999). ATP-dependent Steps in Apoptotic Signal Transduction. Cancer Res. 59: 2174-2181 [Abstract] [Full Text]  
• Heerdt, B. G., Houston, M. A., Anthony, G. M., Augenlicht, L. H. (1999). Initiation of Growth Arrest and Apoptosis of MCF-7 Mammary Carcinoma Cells by Tributyrin, a Triglyceride Analogue of the Short-Chain Fatty Acid Butyrate,Is Associated with Mitochondrial Activity. Cancer Res. 59: 1584-1591 [Abstract] [Full Text]  
• Ushmorov, A., Ratter, F., Lehmann, V., Droge, W., Schirrmacher, V., Umansky, V. (1999). Nitric Oxide-Induced Apoptosis in Human Leukemic Lines Requires Mitochondrial Lipid Degradation and Cytochrome C Release. Blood 93: 2342-2352 [Abstract] [Full Text]  
• Li, R., Pei, H., Papas, T. (1999). The p42 variant of ETS1 protein rescues defective Fas-induced apoptosis in colon carcinoma cells. Proc. Natl. Acad. Sci. USA 96: 3876-3881 [Abstract] [Full Text]  
• Chien, M. M., Zahradka, K. E., Newell, M. K., Freed, J. H. (1999). Fas-induced B Cell Apoptosis Requires an Increase in Free Cytosolic Magnesium as an Early Event. J. Biol. Chem. 274: 7059-7066 [Abstract] [Full Text]  
• Fu, W., Begley, J. G., Killen, M. W., Mattson, M. P. (1999). Anti-apoptotic Role of Telomerase in Pheochromocytoma Cells. J. Biol. Chem. 274: 7264-7271 [Abstract] [Full Text]  
• Kerr, P. M., Suleiman, M.-S., Halestrap, A. P. (1999). Reversal of permeability transition during recovery of hearts from ischemia and its enhancement by pyruvate. Am. J. Physiol. Heart Circ. Physiol. 276: H496-H502 [Abstract] [Full Text]  
• Banki, K., Hutter, E., Gonchoroff, N. J., Perl, A. (1999). Elevation of Mitochondrial Transmembrane Potential and Reactive Oxygen Intermediate Levels Are Early Events and Occur Independently from Activation of Caspases in Fas Signaling. J. Immunol. 162: 1466-1479 [Abstract] [Full Text]  
• Susin, S. A., Lorenzo, H. K., Zamzami, N., Marzo, I., Brenner, C., Larochette, N., Prevost, M.-C., Alzari, P. M., Kroemer, G. (1999). Mitochondrial Release of Caspase-2 and -9 during the Apoptotic Process. JEM 189: 381-394 [Abstract] [Full Text]  
• Yamashita, K., Takahashi, A., Kobayashi, S., Hirata, H., Mesner, P. W. Jr, Kaufmann, S. H., Yonehara, S., Yamamoto, K., Uchiyama, T., Sasada, M. (1999). Caspases Mediate Tumor Necrosis Factor-alpha -Induced Neutrophil Apoptosis and Downregulation of Reactive Oxygen Production. Blood 93: 674-685 [Abstract] [Full Text]  
• MacDonald, G., Shi, L., Velde, C. V., Lieberman, J., Greenberg, A. H. (1999). Mitochondria-dependent and -independent Regulation of Granzyme B-induced Apoptosis. JEM 189: 131-144 [Abstract] [Full Text]  
• Yang, X., Stennicke, H. R., Wang, B., Green, D. R., Janicke, R. U., Srinivasan, A., Seth, P., Salvesen, G. S., Froelich, C. J. (1998). Granzyme B Mimics Apical Caspases. DESCRIPTION OF A UNIFIED PATHWAY FOR TRANS-ACTIVATION OF EXECUTIONER CASPASE-3 AND -7. J. Biol. Chem. 273: 34278-34283 [Abstract] [Full Text]  
• Narita, M., Shimizu, S., Ito, T., Chittenden, T., Lutz, R. J., Matsuda, H., Tsujimoto, Y. (1998). Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria. Proc. Natl. Acad. Sci. USA 95: 14681-14686 [Abstract] [Full Text]  
• Steemans, M., Goossens, V., Van de Craen, M., Van Herreweghe, F., Vancompernolle, K., De Vos, K., Vandenabeele, P., Grooten, J. (1998). A Caspase-activated Factor (CAF) Induces Mitochondrial Membrane Depolarization and Cytochrome c Release by a Nonproteolytic Mechanism. JEM 188: 2193-2198 [Abstract] [Full Text]  
• Fuller, C. L., Braciale, V. L. (1998). Selective Induction of CD8+ Cytotoxic T Lymphocyte Effector Function by Staphylococcus Enterotoxin B. J. Immunol. 161: 5179-5186 [Abstract] [Full Text]  

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