Abstract
Traditionally, mitochondria have been viewed as the “powerhouse” of the cell, i.e., the site of theoxidative phosphorylation machinery involved in ATP production. Consequently, much of theresearch conducted on mitochondria over the past 4 decades has focused on elucidating both thosemolecular events involved in ATP synthesis by oxidative phosphorylation and those involved inthe biogenesis of the oxidative phosphorylation machinery. While monumental achievements havebeen made, and continue to be made, in the study of these remarkable but extremely complexprocesses essential for the life of most animal cells, it has been only in recent years that a largebody of biological and biomedical scientists have come to recognize that mitochondria participatein other important processes. Two of these are cell death and aging which, not surprisingly, are relatedprocesses both involving, in part, the oxidative phosphorylation machinery. This new awareness hassparked a new and growing area of mitochondrial research, that has become of great interest to awide variety of scientists ranging from those involved in elucidating the role of mitochondria incell death and aging to those interested in either suppressing or facilitating these processes as itrelates to identifying new therapies or drugs for human disease. It is the purpose of this briefintroductory review to provide an overview of those mitochondrial events involved in the life anddeath of animal cells and to indicate how these events might relate to the human aging process.Much more is known, much remains controversial, and even more remains to be learned as indicatedin the excellent set of minireviews that follow.
REFERENCES
Abrahams, J. B., Leslie, A. G. W., Lutter, R., and Walker, J. E. (1994) Nature (London) 370, 621-628.
Anson, R. M., Croteau, D. L., Stierum, R. H., Filburn, C., Parsell, R., and Bohr, V. A. (1998). Nucleic Acid Res. 26, 662-668.
Autor, A. P. (1982). J. Biol. Chem. 257, 2713-2718.
Bianchet, M. A., Hullihen, J., Pedersen, P. L., and Amzel, L. M. (1998). Proc. Natl. Acad. Sci. U.S. 95, 11065-11070.
Barja, G. (1999). J. Bioenerg. and Biomembr. 31, 347-366.
Barja, G. and Herrero, A. (1998). J. Bioenerg. Biomemb. 30, 235-243.
Barrientos, A., Casademont, J., Rotig, A., Miro, O., Urbano-Marquez, A., Rustin, P., and Cardellach, F. (1996). Biochem. Biophys. Res. Commun. 229,536-539.
Bohr, V. A., and Anson, R. M. (1999). J. Bioenerg. Biomemb. 31, 391-398.
Boveris, A., and Chance, B. (1973). Biochem. J. 134, 707-716.
Boyer, P. D. (1997). Annu. Rev. Biochem. 66, 714-749.
Brierley, E. J., Johnson, M. A., Bowman, A., Ford, G. A., Subhan, F., Reed, J. W., James, O. F. W., and Turnbull, D. M. (1997). Ann. of Neurol. 41, 114-116.
Brzenzinshi, P., and Adelroth, P. (1998). J. Bioenerg. Biomemb. 30, 99-107.
Cai, J., and Jones, D. P. (1999). J. Bioenerg. Biomembr. 31, 327-334.
Cai, J., Yang, J., and Jones, D. P. (1998). Biochim. Biophys. Acta 1366, 139-149.
Catterall, W. A., and Pedersen, P. L. (1971). J. Biol. Chem. 246, 4987-4994.
Catterall, W. A., Coty, W. A., and Pedersen, P. L. (1973). J. Biol. Chem. 248, 7427-7431.
Chance, B., Sies, H., and Boveris, A. (1979). Physiol. Rev. 59, 527-605.
Clayton, D. A., Doda, J. N., and Friedberg, E. C. (1974). Proc. Nat. Acad. Sci. (U.S.) 71, 2777-2781.
Cortopassi, G. A., and Wong, A. (1999). Biochim. Biophys. Acta 1410, 183-193.
Cory, S., Vaux, D. L., Strasser, A., Harris, A. W., and Adams, J. M. (1999). Cancer Res. (Suppl.) 59, 1685s-1692s.
Cross, R. L. (1981). Annu. Rev. Biochem. 50, 681-714.
Cross, R. L., Grubmeyer, C., and Penefsky, H. S. (1982). J. Biol. Chem. 257, 12101-12105.
Di Lisa, F., Menabo, R., Canton, M., and Petronilli, V. (1998). Biochim. Biophys. Acta 1366, 69-78.
Dizdaroglu, M. (1991). Free Radical Biol. Med. 10, 225-242.
Dmitriev, O. Y., Jons, P. C., and Fillingame, R. H. (1999). Proc. Natl. Acad. Sci. U.S. 96, 7785-7790.
Duncan, T. M., Bulygin, V. V., Zhou, Y., Hutcheon, M. L., and Cross, R. L. (1995). Proc. Natl. Acad. Sci. U.S. 92, 10964-10968.
Engelbrecht, S., and Junge, W. (1997). FEBS Lett. 414, 485-491.
Fontaine, E., and Bernardi, P. (1999). J. Bioenerg. Biomemb. 31, 335-345.
Geller-Lipsky, N., and Pedersen, P. L. (1981). J. Biol. Chem. 256, 8652-8657.
Geller-Lipsky, N., and Pedersen, P. L. (1982). J. Biol. Chem. 257, 1473-1481.
Harman, D. (1956). J. Gerontol. 11, 298-300.
Harman, D. (1983). Age 6, 86-94.
Hayakawa, M., Torri, K., Sugiyama, S., Tanaka, M., and Ozawa, T. (1991). Biochem. Biophys. Res. Commun. 179, 1023-1029.
Hatefi, Y. (1985). Annu. Rev. Biochem. 54, 1015-1069.
Haworth, R. A., and Hunter, D. R. (1979). Arch. Biochem. Biophys. 195, 460-467.
Heiskanen, K. M., Bhat, M. B., Wang, H. W., Ma, J., and Neiminen, A. L. (1999). J. Biol. Chem. 274, 5654-5658.
Holinger, E. P., Chittenden, T., and Lutz, R. J. (1999). J. Biol. Chem. 274, 13298-13304.
Iwata, S., Ostermeier, C., Ludwig, B., and Michel, H. (1995). Nature (London) 376, 660-669.
Iwata, S., Lee, J. W., Okada, K., Lee, J. K., Iwata, M., Rasmussen. B., Link, T. A., Ramaswamy, S., and Jap, B. K. (1998). Science 281, 64-71.
Jiang, S., Cai, J., Wallace, D. C., and Jones, D. P. (1999). J. Biol. Chem. 274, 29905-29911.
Karrasch, S. and Walker, J. E. (1999). J. Mol. Biol. 290, 379-384.
Kato-Yamada, Y., Noji, H., Yasuda, R., Kinosita, K. Jr., and Yoshida, M. (1998). J. Biol. Chem. 273, 19375-19377.
Kerr, J. F. R., Wyllie, A. H., and Currie, A. R. (1972). Brit. J. Cancer 26, 239-245.
Kirsch, D. G., Doseff, A., Chau, B. N., Lim, D.-S., de Souza-Pinto, N. C., Hansford, R., Kastan, M. B., Lazebnik, Y. A., and Hardwick, J. M. (1999). J. Biol. Chem. 274, 21155-21161.
Kluck, R. M., Bossy-Wetzel, E., Green, D. R., and Newmeyer, D. D. (1997). Science 275, 1132-1136.
Korsmeyer, S. J. (1999). Cancer Res. (Suppl.) 59, 1693s-1700s.
Lebowitz, M. S., and Pedersen, P. L. (1996). Arch. Biochem. Biophys. 330, 342-354.
Lehninger A. L. (1964). The Mitochondrion (Benjamin, New York), pp. 1-4.
Lemasters, J. J., Nieminen, A.-L., Qia, T., Trost, L. C., Elmore, S. P., Nishimura, Y., Crowe, R. A., Cascio, W. E., Bradham, C. A., Brenner. D. A., and Herman, B. (1998). Biochim. Biophys. Acta. 1366, 177-196.
Lemasters, J. J., Quian, T., Bradham, C. A., Brenner, D. A., Cascio, W. E., Trost, L. C., Nichimura, Y., Nieminen, A.-L., and Herman, B. (1999). J. Bioenerg. Biomemb. 31, 305-319.
Lenaz, G. (1998). Biochim. Biophys. Acta 1366, 53-67.
Li, H., Zhu, H., Xu, C.-J., and Yuan, J. (1998). Cell 94, 491-501.
Linnane, A. W., Marsuki, S. Ozawa, T., and Tanaka, M. (1989). Lancet 1, 642-645.
Liu, X., Kim, C. N., Yang, J., Jemmerson, R., and Wang, X. (1996). Cell 86, 147-157.
Liu, S. (1999). J. Bioenerg. Biomembr. 31, 367-376.
Luo, X, Budihardjo, I., Zou, H., Slaughter, C., and Wang, X. (1998). Cell 94, 481-490.
Matsuno-Yagi, A. and Hatefi, Y. (1996). J. Biol. Chem. 271, 6164-6171.
Matsuyama, S., Xu, Q., Velours, J., and Reed, J. C. (1998). Mol. Cell, pp. 327-336.
Mecocci, P. and MacGarvey, U. (1994). Ann. Neurol. 36, 747-751.
Mecocci, P., MacGarvey, U., Kaufman, A. E., Koontz, D., Shoffner, J. M., Wallace, D. C.,and Beal, M. F. (1993). Ann. Neurol. 34, 609-616.
Miquel, J., and Fleming, J. E. (1984). Exp. Gerontol. 19, 31-36.
Miquel, J., Economos, A. C., Fleming, J. E., and Johnson, J. E., Jr. (1980). Exp. Gerontol. 15, 575-591.
Montal, M. (1998). Biochim. Biophys. Acta 1366, 113-126.
Munn, E. L. (1974). The Structure of Mitochondria (Academic Press, New York), pp. 1-129.
Nakashima, R. A., Paggi, M. G., and Pedersen, P. L. (1984). Cancer Res. 44, 5702-5706.
Nicholls, D. G. (1982). Bioenergetics (Academic Press, New York), pp.93-95.
Noji, H., Yasuda, R., Yoshida, M., and Kinosita, K., Jr. (1997). Nature (London) 386, 299-302.
Nunez, G., Benedict, M. A., Hu, Y., and Inohara, N. (1998). Oncogene 17, 3237-3245.
Ozawa, T. (1995). Biochem. Biophys. Acta 1271, 177-189.
Ozawa, T. (1997). Physiol. Rev. 77, 425-464.
Ozawa, T. (1999). J. Bioenerg. Biomembr. 31, 377-390.
Ozawa, T., Katsumata, K., Hayakawa, M., Tanaka, M., Sugiyama, S., Tanaka, T., Itoyama, S., Nunoda, S., and Sekigukchi, M (1995). Biochem. Biophys. Res. Commun. 207, 613-620.
Oshino, N., and Chance, B. (1977). Biochem. J. 162, 509-525.
Pan, W., Ko, Y. H., and Pedersen, P. L. (1998). Biochemistry 37, 6911-6923.
Pedersen, P. L. (1996). J. Bioenerg. Biomembr. 28, 389-395.
Pedersen, P. L. (1997). Encyclopedia of Human Biology, 2nd edn., Vol. 1 (Academic Press, New York), pp. 575-583.
Reed, J. C., Jurgensmeier, M., and Matsuyama, S. (1998). Biochim. Biophys. Acta 1366, 127-137.
Reynafarje, B. D., and Pedersen, P. L. (1996). J. Biol. Chem. 271, 32546-32550.
Richter, C. (1988). FEBS Lett. 241, 1-5.
Rouslin, W. (1988). J. Mol. Cell Cardiol. 20, 999-1007.
Saraste, M. (1999). Science 283, 1488-1493.
Schnaitman, C. A., and Greenawalt, J. W. (1968). J. Cell Biol. 38,158-175.
Schwerzmann, K., and Pedersen, P. L. (1986). Arch. Biochem. Biophys. 250, 1-18.
Shaham, S., Shuman, M. A., and Herskowitz, I. (1998). Cell 92, 425-427.
Shigengaga, M. K., and Ames, B. N. (1991). Free Radical Biol. Med. 10, 211-216.
Shigenaga, M. K., Hagen, T. M., and Ames, B. N. (1994). Proc. Natl. Acad. Sci. U.S. 91, 10771-10778.
Shirakihara, Y., Leslie, A. G. W., Abrahams, J. P., Walker, J. E., Udea, T., Sekimato, Y., Kambara, M., Saika, K., Kagawa, Y., and Yoshida, M. (1997). Structure 5, 825-836.
Skulachev, V. P. (1996). FEBS Lett. 397, 7-10.
Srinivasula, S. M., Ahmad, M., Ferandes-Alnemri, Litwack, G., and Alnemri, E. S. (1996). Proc. Natl. Acad. Sci. U.S. 93, 14486-14491.
Susin, S. A., Zamzami, N., and Kroemer, G. (1998). Biochim. Biophys. Acta 1366, 151-165.
Trumpower, B. L. (1990). J. Biol. Chem. 265, 11409-11412.
Tsukihara, T., Aoyama, H., Yamashita, E., Tomizaki, T., Yamaguchi, H., Shinzawa-Itol, K., Nakashima, R., Yaono, R., and Yoshikawa, S. (1995). Science 269,1069-1074.
Vik, S. B., and Antonio, B. J. (1994). J. Biol. Chem. 269, 30364-30369.
Wallace, D. C. (1992). Science 256, 628-632.
Wallace, D. C. (1994). J. Bioenerg. Biomembr. 26, 241-250.
Wallace, D. C. (1999). Science 283, 1482-1488.
Walker, J. (1994). Current Opin. Struct. Biol. 4, 912-918.
Weber, J., and Senior, A. E. (1997). Biochem. Biophys. Acta 1319,19-58.
Wilkens, S., and Capaldi, R. A. (1998). Nature (London) 393, 29.
Wispe, J. R., Clark, J. C., Burhams, M. S., Kropp, K. E., Korfhagen, T. R., and Whitsett, J. A. (1989). Biochim. Biophys. Acta 994, 30-36.
Wyllie, A. H. (1980). Nature (London) 284, 555-556.
Xia, D., Yu, C.-A., Kim, H., Xia, J.-Z., Kachurin, A. M., Zhang, L., Yu, L., and Deisenhofer, J. (1997). Science 277, 60-66.
Yang, J., Liu, X., Bhalla, K., Kim, C. N., Ibrado, A. M., Cai, J., Peng, T.-I., Jones, D. P., and Wang, X. (1997). Science 275, 1129-1132.
Yoneda, M., Katsumata, K., Hayakawa, M., Tanaka, M., and Ozawa, T. (1995). Biochem. Biophys. Res. Commun. 209, 723-729.
Zoratti, M., and Szabo, I. (1995). Biochim. Biophys. Acta 1241, 139-176.
Zhang, Z., Huang, L., Shulmeister, V. M., Chi, Y.-I., Kim, K.-K., Hung, L.-W., Crofts, A. R., Berry, E. A., and Kim, S.-H. (1998). Nature (London) 392, 677-687.
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Pedersen, P.L. Mitochondrial Events in the Life and Death of Animal Cells: A Brief Overview. J Bioenerg Biomembr 31, 291–304 (1999). https://doi.org/10.1023/A:1005453700533
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DOI: https://doi.org/10.1023/A:1005453700533