J. Exp. Med., Volume 187, Number 8, April 20, 1998 1261-1271

The Permeability Transition Pore Complex: A Target for Apoptosis Regulation by Caspases and Bcl-2-related Proteins

By Isabel Marzo,^* Catherine Brenner,^* Naoufal Zamzami,^* Santos A. Susin,^* Gisela Beutner, Dieter Brdiczka, René Rémy,^§ Zhi-Hua Xie, John C. Reed, and Guido Kroemer^*

From the ^* Centre National de la Recherche Scientifique, Unité Propre de Recherche 420, F-94801 Villejuif, France; the  Faculty of Biology, University of Konstanz, D-78434 Konstanz, Germany; the ^§ Centre National de la Recherche Scientifique, Université de Paris 11, F-91405 Orsay, France; and  The Burnham Institute, La Jolla, California 92037

Early in programmed cell death (apoptosis), mitochondrial membrane permeability increases. This is at least in part due to opening of the permeability transition (PT) pore, a multiprotein complex built up at the contact site between the inner and the outer mitochondrial membranes. The PT pore has been previously implicated in clinically relevant massive cell death induced by toxins, anoxia, reactive oxygen species, and calcium overload. Here we show that PT pore complexes reconstituted in liposomes exhibit a functional behavior comparable with that of the natural PT pore present in intact mitochondria. The PT pore complex is regulated by thiol-reactive agents, calcium, cyclophilin D ligands (cyclosporin A and a nonimmunosuppressive cyclosporin A derivative), ligands of the adenine nucleotide translocator, apoptosis-related endoproteases (caspases), and Bcl-2-like proteins. Although calcium, prooxidants, and several recombinant caspases (caspases 1, 2, 3, 4, and 6) enhance the permeability of PT pore-containing liposomes, recombinant Bcl-2 or Bcl-X_L augment the resistance of the reconstituted PT pore complex to pore opening. Mutated Bcl-2 proteins that have lost their cytoprotective potential also lose their PT modulatory capacity. In conclusion, the PT pore complex may constitute a crossroad of apoptosis regulation by caspases and members of the Bcl-2 family.

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• Katz, E., Lord, C., Ford, C. A., Gauld, S. B., Carter, N. A., Harnett, M. M. (2004). Bcl-xL antagonism of BCR-coupled mitochondrial phospholipase A2 signaling correlates with protection from apoptosis in WEHI-231 B cells. Blood 103: 168-176 [Abstract] [Full Text]  
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• Luciakova, K., Barath, P., Poliakova, D., Persson, A., Nelson, B. D. (2003). Repression of the Human Adenine Nucleotide Translocase-2 Gene in Growth-arrested Human Diploid Cells: THE ROLE OF NUCLEAR FACTOR-1. J. Biol. Chem. 278: 30624-30633 [Abstract] [Full Text]  
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• Crow, M. T. (2002). Hypoxia, BNip3 Proteins, and the Mitochondrial Death Pathway in Cardiomyocytes. Circ. Res. 91: 183-185 [Full Text]  
• Werner, E., Werb, Z. (2002). Integrins engage mitochondrial function for signal transduction by a mechanism dependent on Rho GTPases. JCB 158: 357-368 [Abstract] [Full Text]  
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• Matarrese, P., Di Biase, L., Santodonato, L., Straface, E., Mecchia, M., Ascione, B., Parmiani, G., Belardelli, F., Ferrantini, M., Malorni, W. (2002). Type I Interferon Gene Transfer Sensitizes Melanoma Cells to Apoptosis via a Target Activity on Mitochondrial Function. Am. J. Pathol. 160: 1507-1520 [Abstract] [Full Text]  
• Kim, K. Y., Kim, B. G., Kim, S.-O., Yoo, S.-E., Kwak, Y.-G., Chae, S.-W., Hong, K. W. (2002). Prevention of Lipopolysaccharide-Induced Apoptosis by (2S,3S,4R)-N""-Cyano-N-(6-amino-3,4-dihydro-3-hydroxy-2-methyl-2-dimethoxymethyl-2H-benzopyran-4-yl)-N'-benzylguanidine, a Benzopyran Analog, in Endothelial Cells. J. Pharmacol. Exp. Ther. 300: 535-542 [Abstract] [Full Text]  
• Kim, K. Y., Shin, H. K., Choi, J. M., Hong, K. W. (2002). Inhibition of Lipopolysaccharide-Induced Apoptosis by Cilostazol in Human Umbilical Vein Endothelial Cells. J. Pharmacol. Exp. Ther. 300: 709-715 [Abstract] [Full Text]  
• Maianski, N. A., Mul, F. P. J., van Buul, J. D., Roos, D., Kuijpers, T. W. (2002). Granulocyte colony-stimulating factor inhibits the mitochondria-dependent activation of caspase-3 in neutrophils. Blood 99: 672-679 [Abstract] [Full Text]  
• Gerasimenko, J. V., Gerasimenko, O. V., Palejwala, A., Tepikin, A. V., Petersen, O. H., Watson, A. J. M. (2002). Menadione-induced apoptosis: roles of cytosolic Ca2+ elevations and the mitochondrial permeability transition pore. J. Cell Sci. 115: 485-497 [Abstract] [Full Text]  
• Schlattner, U., Dolder, M., Wallimann, T., Tokarska-Schlattner, M. (2001). Mitochondrial Creatine Kinase and Mitochondrial Outer Membrane Porin Show a Direct Interaction That Is Modulated by Calcium. J. Biol. Chem. 276: 48027-48030 [Abstract] [Full Text]  
• Wasilenko, S. T., Meyers, A. F. A., Vander Helm, K., Barry, M. (2001). Vaccinia Virus Infection Disarms the Mitochondrion-Mediated Pathway of the Apoptotic Cascade by Modulating the Permeability Transition Pore. J. Virol. 75: 11437-11448 [Abstract] [Full Text]  
• Cheng, A., Chan, S. L., Milhavet, O., Wang, S., Mattson, M. P. (2001). p38 MAP Kinase Mediates Nitric Oxide-induced Apoptosis of Neural Progenitor Cells. J. Biol. Chem. 276: 43320-43327 [Abstract] [Full Text]  
• Park, I.-W., Ullrich, C. K., Schoenberger, E., Ganju, R. K., Groopman, J. E. (2001). HIV-1 Tat Induces Microvascular Endothelial Apoptosis Through Caspase Activation. J. Immunol. 167: 2766-2771 [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]  
• JAYANTHI, S., DENG, X., BORDELON, M., MCCOY, M. T., CADET, J. L. (2001). Methamphetamine causes differential regulation of pro-death and anti-death Bcl-2 genes in the mouse neocortex. FASEB J. 15: 1745-1752 [Abstract] [Full Text]  
• Pardo, J., Perez-Galan, P., Gamen, S., Marzo, I., Monleon, I., Kaspar, A. A., Susin, S. A., Kroemer, G., Krensky, A. M., Naval, J., Anel, A. (2001). A Role of the Mitochondrial Apoptosis-Inducing Factor in Granulysin-Induced Apoptosis. J. Immunol. 167: 1222-1229 [Abstract] [Full Text]  
• Gain, P., Thuret, G., Chiquet, C., Dumollard, J. M., Mosnier, J. F., Campos, L. (2001). In situ immunohistochemical study of Bcl-2 and heat shock proteins in human corneal endothelial cells during corneal storage. Br. J. Ophthalmol. 85: 996-1000 [Abstract] [Full Text]  
• Nakao, Y., Otani, H., Yamamura, T., Hattori, R., Osako, M., Imamura, H. (2001). Insulin-like growth factor 1 prevents neuronal cell death and paraplegia in the rabbit model of spinal cord ischemia. J. Thorac. Cardiovasc. Surg. 122: 136-143 [Abstract] [Full Text]  
• Haridas, V., Higuchi, M., Jayatilake, G. S., Bailey, D., Mujoo, K., Blake, M. E., Arntzen, C. J., Gutterman, J. U. (2001). Avicins: Triterpenoid saponins from Acacia victoriae (Bentham) induce apoptosis by mitochondrial perturbation. Proc. Natl. Acad. Sci. USA 98: 5821-5826 [Abstract] [Full Text]  
• Waterhouse, N. J., Goldstein, J. C., von Ahsen, O., Schuler, M., Newmeyer, D. D., Green, D. R. (2001). Cytochrome c Maintains Mitochondrial Transmembrane Potential and ATP Generation after Outer Mitochondrial Membrane Permeabilization during the Apoptotic Process. JCB 153: 319-328 [Abstract] [Full Text]  
• Subrahmanyam, Y. V. B. K., Yamaga, S., Prashar, Y., Lee, H. H., Hoe, N. P., Kluger, Y., Gerstein, M., Goguen, J. D., Newburger, P. E., Weissman, S. M. (2001). RNA expression patterns change dramatically in human neutrophils exposed to bacteria. Blood 97: 2457-2468 [Abstract] [Full Text]  
• LONGONI, B., BOSCHI, E., DEMONTIS, G. C., RATTO, G. M., MOSCA, F. (2001). Apoptosis and adaptive responses to oxidative stress in human endothelial cells exposed to cyclosporin A correlate with BCL-2 expression levels. FASEB J. 15: 731-740 [Abstract] [Full Text]  
• Yamamura, T., Otani, H., Nakao, Y., Hattori, R., Osako, M., Imamura, H. (2001). IGF-I differentially regulates Bcl-xL and Bax and confers myocardial protection in the rat heart. Am. J. Physiol. Heart Circ. Physiol. 280: H1191-H1200 [Abstract] [Full Text]  
• Belzacq, A.-S., Jacotot, E., Vieira, H. L. A., Mistro, D., Granville, D. J., Xie, Z., Reed, J. C., Kroemer, G., Brenner, C. (2001). Apoptosis Induction by the Photosensitizer Verteporfin: Identification of Mitochondrial Adenine Nucleotide Translocator as a Critical Target. Cancer Res. 61: 1260-1264 [Abstract] [Full Text]  
• Takada, E., Toyota, H., Suzuki, J., Mizuguchi, J. (2001). Prevention of Anti-IgM-Induced Apoptosis Accompanying G1 Arrest in B Lymphoma Cells Overexpressing Dominant-Negative Mutant Form of c-Jun N-Terminal Kinase 1. J. Immunol. 166: 1641-1649 [Abstract] [Full Text]  
• Katz, E., Deehan, M. R., Seatter, S., Lord, C., Sturrock, R. D., Harnett, M. M. (2001). B Cell Receptor-Stimulated Mitochondrial Phospholipase A2 Activation and Resultant Disruption of Mitochondrial Membrane Potential Correlate with the Induction of Apoptosis in WEHI-231 B Cells. J. Immunol. 166: 137-147 [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]  
• Crompton, M. (2000). Mitochondrial intermembrane junctional complexes and their role in cell death. J. Physiol. 529: 11-21 [Abstract] [Full Text]  
• O'Rourke, B. (2000). Pathophysiological and protective roles of mitochondrial ion channels. J. Physiol. 529: 23-36 [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]  
• 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]  
• Kowaltowski, A. J., Smaili, S. S., Russell, J. T., Fiskum, G. (2000). Elevation of resting mitochondrial membrane potential of neural cells by cyclosporin A, BAPTA-AM, and Bcl-2. Am. J. Physiol. Cell Physiol. 279: C852-C859 [Abstract] [Full Text]  
• Hiura, T. S., Li, N., Kaplan, R., Horwitz, M., Seagrave, J.-C., Nel, A. E. (2000). The Role of a Mitochondrial Pathway in the Induction of Apoptosis by Chemicals Extracted from Diesel Exhaust Particles. J. Immunol. 165: 2703-2711 [Abstract] [Full Text]  
• Khoshnan, A., Tindell, C., Laux, I., Bae, D., Bennett, B., Nel, A. E. (2000). The NF-{kappa}B Cascade Is Important in Bcl-xL Expression and for the Anti-Apoptotic Effects of the CD28 Receptor in Primary Human CD4+ Lymphocytes. J. Immunol. 165: 1743-1754 [Abstract] [Full Text]  
• Vande Velde, C., Cizeau, J., Dubik, D., Alimonti, J., Brown, T., Israels, S., Hakem, R., Greenberg, A. H. (2000). BNIP3 and Genetic Control of Necrosis-Like Cell Death through the Mitochondrial Permeability Transition Pore. Mol. Cell. Biol. 20: 5454-5468 [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]  
• Wang, J.-L., Liu, D., Zhang, Z.-J., Shan, S., Han, X., Srinivasula, S. M., Croce, C. M., Alnemri, E. S., Huang, Z. (2000). Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells. Proc. Natl. Acad. Sci. USA 97: 7124-7129 [Abstract] [Full Text]  
• Saldeen, J. (2000). Cytokines Induce Both Necrosis and Apoptosis via a Common Bcl-2-Inhibitable Pathway in Rat Insulin-Producing Cells. Endocrinology 141: 2003-2010 [Abstract] [Full Text]  
• Haraguchi, M., Torii, S., Matsuzawa, S.-i., Xie, Z., Kitada, S., Krajewski, S., Yoshida, H., Mak, T. W., Reed, J. C. (2000). Apoptotic Protease Activating Factor 1 (Apaf-1)-independent Cell Death Suppression by Bcl-2. JEM 191: 1709-1720 [Abstract] [Full Text]  
• Perlman, H., Georganas, C., Pagliari, L. J., Koch, A. E., Haines, K. III, Pope, R. M. (2000). Bcl-2 Expression in Synovial Fibroblasts Is Essential for Maintaining Mitochondrial Homeostasis and Cell Viability. J. Immunol. 164: 5227-5235 [Abstract] [Full Text]  
• Hausmann, G., O'Reilly, L. A., van Driel, R., Beaumont, J. G., Strasser, A., Adams, J. M., Huang, D. C.S. (2000). Pro-apoptotic Apoptosis Protease-activating Factor 1 (Apaf-1) Has a Cytoplasmic Localization Distinct from Bcl-2 or Bcl-xL. JCB 149: 623-634 [Abstract] [Full Text]  
• Gross, A., Pilcher, K., Blachly-Dyson, E., Basso, E., Jockel, J., Bassik, M. C., Korsmeyer, S. J., Forte, M. (2000). Biochemical and Genetic Analysis of the Mitochondrial Response of Yeast to BAX and BCL-XL. Mol. Cell. Biol. 20: 3125-3136 [Abstract] [Full Text]  
• DAUGAS, E., SUSIN, S. A., ZAMZAMI, N., FERRI, K. F., IRINOPOULOU, T., LAROCHETTE, N., PRÉVOST, M.-C., LEBER, B., ANDREWS, D., PENNINGER, J., KROEMER, G. (2000). Mitochondrio-nuclear translocation of AIF in apoptosis and necrosis. FASEB J. 14: 729-739 [Abstract] [Full Text]  
• Hsu, S. Y., Hsueh, A. J. W. (2000). Tissue-Specific Bcl-2 Protein Partners in Apoptosis: An Ovarian Paradigm. Physiol. Rev. 80: 593-614 [Abstract] [Full Text]  
• Rahmani, Z., Huh, K.-W., Lasher, R., Siddiqui, A. (2000). Hepatitis B Virus X Protein Colocalizes to Mitochondria with a Human Voltage-Dependent Anion Channel, HVDAC3, and Alters Its Transmembrane Potential. J. Virol. 74: 2840-2846 [Abstract] [Full Text]  
• Hirpara, J. L., Seyed, M. A., Loh, K. W., Dong, H., Kini, R. M., Pervaiz, S. (2000). Induction of mitochondrial permeability transition and cytochrome C release in the absence of caspase activation is insufficient for effective apoptosis in human leukemia cells. Blood 95: 1773-1780 [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]  
• Bauer, M. K.A., Schubert, A., Rocks, O., Grimm, S. (1999). Adenine Nucleotide Translocase-1, a Component of the Permeability Transition Pore, Can Dominantly Induce Apoptosis. JCB 147: 1493-1502 [Abstract] [Full Text]  
• HORTELANO, S., ALVAREZ, A. M., BOSCÁ, L. (1999). Nitric oxide induces tyrosine nitration and release of cytochrome c preceding an increase of mitochondrial transmembrane potential in macrophages. FASEB J. 13: 2311-2317 [Abstract] [Full Text]  
• O’Rourke, B. (1999). Apoptosis : Rekindling the Mitochondrial Fire. Circ. Res. 85: 880-883 [Full Text]  
• Erkkilä, K., Pentikäinen, V., Wikström, M., Parvinen, M., Dunkel, L. (1999). Partial Oxygen Pressure and Mitochondrial Permeability Transition Affect Germ Cell Apoptosis in the Human Testis. J. Clin. Endocrinol. Metab. 84: 4253-4259 [Abstract] [Full Text]  
• Reed, J. C. (1999). Dysregulation of Apoptosis in Cancer. JCO 17: 2941-2941 [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]  
• 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]  
• Dallaporta, B., Marchetti, P., de Pablo, M. A., Maisse, C., Duc, H.-T., Metivier, D., Zamzami, N., Geuskens, M., Kroemer, G. (1999). Plasma Membrane Potential in Thymocyte Apoptosis. J. Immunol. 162: 6534-6542 [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]  
• Zhu, X.-H., Shen, Y.-L., Jing, Y.-k., Cai, X., Jia, P.-M., Huang, Y., Tang, W., Shi, G.-Y., Sun, Y.-P., Dai, J., Wang, Z.-Y., Chen, S.-J., Zhang, T.-D., Waxman, S., Chen, Z., Chen, G.-Q. (1999). Apoptosis and Growth Inhibition in Malignant Lymphocytes After Treatment With Arsenic Trioxide at Clinically Achievable Concentrations. JNCI J Natl Cancer Inst 91: 772-778 [Abstract] [Full Text]  
• Perez, G. I., Tao, X.-J., Tilly, J. L. (1999). Fragmentation and death (a.k.a. apoptosis) of ovulated oocytes. Mol Hum Reprod 5: 414-420 [Abstract] [Full Text]  
• Fujimura, M., Morita-Fujimura, Y., Kawase, M., Copin, J.-C., Calagui, B., Epstein, C. J., Chan, P. H. (1999). Manganese Superoxide Dismutase Mediates the Early Release of Mitochondrial Cytochrome C and Subsequent DNA Fragmentation after Permanent Focal Cerebral Ischemia in Mice. J. Neurosci. 19: 3414-3422 [Abstract] [Full Text]  
• Hotchkiss, R. S., Swanson, P. E., Knudson, C. M., Chang, K. C., Cobb, J. P., Osborne, D. F., Zollner, K. M., Buchman, T. G., Korsmeyer, S. J., Karl, I. E. (1999). Overexpression of Bcl-2 in Transgenic Mice Decreases Apoptosis and Improves Survival in Sepsis. J. Immunol. 162: 4148-4156 [Abstract] [Full Text]  
• Warny, M., Kelly, C. P. (1999). Monocytic cell necrosis is mediated by potassium depletion and caspase-like proteases. Am. J. Physiol. Cell Physiol. 276: C717-C724 [Abstract] [Full Text]  
• Barath, P., Albert-Fournier, B., Luciakova, K., Nelson, B. D. (1999). Characterization of a Silencer Element and Purification of a Silencer Protein That Negatively Regulates the Human Adenine Nucleotide Translocator 2 Promoter. J. Biol. Chem. 274: 3378-3384 [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]  
• Fulda, S., Scaffidi, C., Susin, S. A., Krammer, P. H., Kroemer, G., Peter, M. E., Debatin, K.-M. (1998). Activation of Mitochondria and Release of Mitochondrial Apoptogenic Factors by Betulinic Acid. J. Biol. Chem. 273: 33942-33948 [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]  
• Matsuyama, S., Schendel, S. L., Xie, Z., Reed, J. C. (1998). Cytoprotection by Bcl-2 Requires the Pore-forming alpha 5 and alpha 6 Helices. J. Biol. Chem. 273: 30995-31001 [Abstract] [Full Text]  

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