Abstract
Mitochondrial permeability transition (PT) involves the formation of proteaceous, regulated pores, probably by apposition of inner and outer mitochondrial membrane proteins which cooperate to form the mitochondrial megachannel (=mitochondrial PT pore). PT has important metabolic consequences, namely the collapse of the mitochondrial transmembrane potential, uncoupling of the respiratory chain, hyperproduction of superoxide anions, disruption of mitochondrial biogenesis, outflow of matrix calcium and glutathione, and release of soluble intermembrane proteins. Recent evidence suggests that PT is a critical, rate limiting event of apoptosis (programmed cell death): (i) induction of PT suffices to cause apoptosis; (ii) one of the immediate consequences of PT, disruption of the mitochondrial transmembrane potential (ΔΨm), is a constant feature of early apoptosis; (iii) prevention of PT impedes the ΔΨm collapse as well as all other features of apoptosis at the levels of the cytoplasma, the nucleus, and the plasma membrane; (iv) PT is modulated by members of the apoptosis-regulatory bcl-2 gene family. Recent data suggest that the acquisition of the apoptotic phenotype, including characteristic changes in nuclear morphology and biochemistry (chromatin condensation and DNA fragmentation), depends on the action of apoptogenic proteins released from the mitochondrial intermembrane space.
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REFERENCES
Golstein, P., Ojcius, D. M. and Young, J. D.-E. (1991) Immunol. Rev. 121:29–65.
Cohen, I. J., Duke, R. C., Fadok, V. A. and Sellins, K. S. (1992) Annu. Rev. Immunol. 10:267–293.
Kroemer, G., Martínez-A., C. and (Editors) (1995) Curr. Top. Microbiol. Immunol. 200:175.
Thompson, C. B. (1995) Science 267:1456–1462.
Kroemer, G., Petit, P. X., Zamzami, N., Vayssière, J.-L. and Mignotte, B. (1995) FASEB J. 9:1277–1287.
Kerr, J. F. R., Wyllie, A. H. and Currie, A. R. (1972) Br. J. Cancer 26:239–257.
Willie, A. H. (1980) Nature 284:555–556.
Jacobson, M. D., Burne, J. F. and Raff, M. C. (1994) EMBO J. 13:1899–1910.
Schulze-Osthoff, K., Walczak, H., Droge, W. and Krammer, P. H. (1994) J. Cell. Biol. 127:15–20.
Nakajima, H., Golstein, P. and Henkart, P. A. (1995) J. Exp. Med. 181:1905–1909.
Castedo, M., Hirsch, T., Susin, S. A., Zamzami, N., Marchetti, P., Macho, A. and Kroemer, G. (1996) J. Immunol. 157:512–521.
Oltvai, Z. N. and Korsmeyer, S. J. (1994) Cell 79:189–192.
Martin, S. J. and Green, D. R. (1995) Cell 82:349–352.
Kroemer, G. and Martínez-A., C. (1994) Immunol. Today 15:235–242.
Kroemer, G. (1995) Adv. Immunol. 58:211–296.
Kane, D. J., Sarafian, T. A., Anton, R., Hahn, H., Gralla, E. B., Valentine, J. S., Örd, T. and Bredesen, D. E. (1993) Science 262:1274–1277.
Martinou, J. C., Dubois-Dauphin-M., Staple, J. K., Rodriguez, I., Frankowski, H., Mlssotten, M., Albertini, P., Talabot, D., Catsikas, S., Pietra, C. and Huarte, J. (1994) Neuron 13:1017–1030.
Shimizu, S., Eguchi, Y., Kamiike, W., Waguri, S., Uchiyama, Y., Matsuda, H. and Tsujimoto, Y. (1996) Oncogene 13:21–29.
Itoh, G., Tamura, J., Suzuki, M., Suzuki, Y., Ikeda, H., Koike, M., Nomura, M., Jie, T. and Ito, K. (1995) Am. J. Pathol 146:1325–1331.
Li, Y., Chopp, M., Jiang, N., Zhang, Z. G. and Zaloga, C. (1995) Stroke 17:1252–1257.
Zamzami, N., Marchetti, P., Castedo, M., Zanin, C., Vayssière, J.-L., Petit, P. X. and Kroemer, G. (1995) J. Exp. Med. 181:1661–1672.
Zamzami, N., Marchetti, P., Castedo, M., Decaudin, D., Macho, A., Hirsch, T., Susin, S. A., Petit, P. X., Mignotte, B. and Kroemer, G. (1995) Exp. Med. 182:367–377.
Castedo, M., Macho, A., Zamzami, N., Hirsch, T., Marchetti, P., Uriel, J. and Kroemer, G. (1995) Eur. J. Immunol. 25:3277–3284.
Zamzami, N., Susin, S. A., Marchetti, P., Hirsch, T., Gómez-Monterrey, I., Castedo, M. and Koremer, G. (1996) J. Exp. Med. 183:1533–1544.
Marchetti, P., Susin, S. A., Decaudin, D., Gamen, S., Castedo, M., Hirsch, T., Zamzami, N., Naval, J., Senik, A. and Kroemer, G. (1996) Cancer Res. 56:2033–2038.
Zamzami, N., Marchetti, P., Castedo, M., Hirsch, T., Susin, S. A., Masse, B. and Kroemer, G. (1996) FEBS Lett. 384:53–57.
Marchetti, P., Castedo, M., Susin, S. A., Zamzami, N., Hirsch, T., Haeffner, A., Hirsch, F., Geuskens, M. and Kroemer, G. (1996) J. Exp. Med. 184:1155–1160.
Susin, S. A., Zamzami, N., Castedo, M., Hirsch, T., Marchetti, P., Macho, A., Daugas, E., Geuskens, M. and Kroemer, G. (1996) J. Exp. Med. 184:1331–1342.
Marchetti, P., Hirsch, T., Zamzami, N., Castedo, M., Decaudin, D., Susin, S. A., Masse, B. and Kroemer, G. (1996) J. Immunol. 157:4830–4836.
Marchetti, P., Zamzami, N., Susin, S. A., Patrice, P. X. and Kroemer, G. (1996) Apoptosis 1:119–125.
Marchetti, P., Decaudin, D., Macho, A., Zamzami, N., Hirsch, T., Susin, S. A. and Kroemer, G. (1996) Eur. J. Immunol. 27:289–296.
Zoratti, M. and Szabò, I. (1995) Biochem. Biophys. Acta-Rev. Biomembranes 1241:139–176.
Bernardi, P. and Petronilli, V. (1996) J. Bioenerg. Biomembr. 28:129–136.
McEnery, M. W., Snowman, A. M., Trifiletti, R. R. and Snyder, S. H. (1992) Proc. Natl. Acad. Sci. USA 89:3170–3174.
Brustovetsky, N. and Klingenberg, M. (1996) Biochemistry 35:8438–8488.
Beutner, G., Rück, A., Riede, B., Welte, W. and Brdiczka, D. (1996) FEBS Lett (in press)
McConkey, D. J., Hartzell, P., Nicotera, P. and Orrenius, S. (1989) FASEB J. 3:1843–1849.
McConkey, D. J., Nicotera, P. and Orrenius, S. (1994) Immunol. Rev. 142:343–363.
Buttke, T. M. and Sandstrom, P. A. (1994) Immunol. Today 15:7–10.
Klingenberg, M. (1980) J. Membrane Biol. 56:97–105.
Costantini, P., Chernyak, B. V., Petronilli, V. and Bernardi, P. (1996) J. Biol. Chem. 271:6746–6751.
Reed, J. C. (1995) J. Cell Biol. 124:1–6.
Yang, E. and Korsmeyer, S. J. (1996) Blood 88:386–401.
Cory, S. (1995) Annu. Rev. Immunol. 13:513–543.
Krajewski, S., Tanaka, S., Takayama, S., Schibler, M. J., Fenton, W. and Reed, J. C. (1993) Cancer Res. 53:4701–4714.
Riparbelli, M. G., Callaini, G., Tripodi, S. A., Cintorino, M., Tosi, P. and Dallai, R. (1995) Exp. Cell Res. 221:363–369.
Gonzalez-Garcia, M., Perez-Ballestero, R., Ding, L. Y., Duan, L., Boise, L. H., Thompson, C. B. and Nuñez, G. (1994) Development 120:3033–3042.
Hickish, T., Robertson, D., Clarke, P., Hill, M., Di-Stefano, F., Clarke, C. and Cunningham, D. (1994) Cancer Res. 54:2808–2811.
Alnemri, E. S., Robertson, N. M., Fernandes, T. F., Croce, C. M. and Litwack, G. (1992) Proc. Natl. Acad. Sci. USA 89:7295–7299.
Tanaka, S., Saito, K. and Reed, J. C. (1993) J. Biol. Chem. 268:10,920–10,926.
Nguyen, M., Branton, P. E., Walton, P. A., Oltvai, Z. N., Korsmeyer, S. J. and Shore, G. C. (1994) J. Biol. Chem. 269:16,521–16,524.
Zhu, W., Cowie, A., Wasfy, G. W., Penn, L. Z., Leber, B. and Andrews, D. W. (1996) EMBO J. 15:4130–4141.
Carayon, P., Portier, M., Dussossoy, D., Bord, A., Petitpretre, G., Canat, X., Le Fur, G. and Casellas, P. (1996) Blood 87:3170–3178.
Baffy, G., Miyashati, T., Williamson, J. R. and Reed, J. C. (1993) J. Biol. Chem. 268:6511–6519.
Liu, X., Kim, C. N., Yang, J., Jemmerson, R. and Wang, X. (1996) Cell 86:147–157.
Kroemer, G., Zamzami, N. and Susin, S. A. (1997) Immunol. Today 18:44–51.
Pastorino, J. G., Simbula, G., Gilfor, E., Hoek, J. B. and Farber, J. B. (1994) J. Biol. Chem. 269:31,041–31,046.
Sato, N., Iwata, S., Nakamura, K., Hori, T., Mori, K. and Yodoi, J. (1995) J. Immunol. 154:3194–3203.
Costantini, P., Chernyak, B. V., Petronilli, V. and Bernardi, P. (1995) FEBS Lett. 362:239–242.
Murphy, A. N., Bredesen, D. E., Cortopassi, G., Wang, E. and Fiskum, G. (1996) Proc. Natl. Acad. Sci. USA 93:9893–9898.
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Hirsch, T., Marzo, I. & Kroemer, G. Role of the Mitochondrial Permeability Transition Pore in Apoptosis. Biosci Rep 17, 67–76 (1997). https://doi.org/10.1023/A:1027339418683
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DOI: https://doi.org/10.1023/A:1027339418683