Abstract
Studies in heart and nonsynaptic brain mitochondria from two mammals and three birds showthat complex I generates oxygen radicals in heart and nonsynaptic brain mitochondria in States4 and 3, whereas complex III does it only in heart mitochondria and only in State 4. Theincrease in oxygen consumption during the State 4 to 3 transition is not accompanied by aproportional increase in oxygen radical generation. This will protect mitochondria and tissuesduring bursts of activity. Comparisons between young and old rodents do not show a consistentpattern of variation in mitochondrial oxygen radical production during aging. However, allthe interspecies comparisons performed to date between different mammals, and betweenmammals and birds, agree that animals with high maximum longevities have low rates ofmitochondrial oxygen radical production, irrespective of the value of their basal specificmetabolic rate. The sites and mechanisms allowing this, the recently described low degree ofmembrane fatty acid unsaturation of longevous animals, and their relation to longevity andaging are discussed.
REFERENCES
Anson, R. M., Croteau, D. L., Stierum, R. H., Fliburn, C., Parsell, R., and Bohr, V. A. (1998). Nucleic Acids Res. 26, 662-668.
Austad, S. N., and Fisher, K. E. (1992). Amer. J. Primatol. 28, 251-261.
Barja, G. (1998). Ann. NY Acad. Sci., 854, 224-238.
Barja, G. (1999). In Methods in Aging Research (Yu, B. P. ed.), CRC Press, Boca Raton, Florida, pp. 533-548.
Barja, G., and Herrero, A. (1998). J. Bioenerg. Biomembr. 30, 235-243.
Barja, G., Cadenas, S., Rojas, C., López-Torres, M., and Pérez-Campo, R. (1994a). Comp. Biochem. Physiol. 108B, 501-512.
Barja, G., Cadenas, S., Rojas, C., Pérez-Campo, R., and López-Torres, M. (1994b). Free Radical Res. 21, 317-328.
Beckman, K. B., and Ames, B. N. (1996). Methods Enzymol. 264, 442-453.
Beckman, K. B., and Ames, B. N. (1998). Physiol. Rev. 78, 547-581.
Boveris, A., and Chance, B. (1973). Biochem. J. 134, 707-716.
Boveris, A., Oshino, N., and Chance, B. (1972). Biochem. J. 128, 617-630.
Boveris, A., Cadenas, E., and Stoppani, A. O. M. (1976). Biochem J. 156, 435-444.
Brand, M. D., and Murphy, M. P. (1987). Biol. Rev. 62, 141-193.
Cadenas, E., and Boveris, A. (1980). Biochem. J. 188, 31-37.
Cadenas, E., Boveris, A., Ragan C. I., and Stoppani, A. O. M. (1977). Arch. Biochem. Biophys. 180, 248-257.
Cadenas, S., Barja, G., Poulsen, H. E., and Loft, S. (1997). Carcinogenesis 18, 2373-2377.
Chance, B. (1981). In Oxygen and Living Processes (Gilbert, D., ed.), Springer Verlag, New York, pp. 200-209.
Chance, B., and Williams, G. R. (1956). Advan. Enzymol. Related Subjects Biochem. 17, 65-134.
Chance, B., and Hollunger, G. J. (1961). J. Biol. Chem. 236, 1534-1543.
Cino, M., and del Maestro, R. F (1989). Arch. Biochem. Biophys. 269, 623-638.
Clayton, D. A., Doda, J. N., and Friedberg, E. C. (1974). Proc. Natl. Acad. Sci. U.S. 71, 2777-2781.
Cortopassi, G. A., and Wang, E. (1996). Mechan. Ageing Develop. 91, 211-218.
Croteau, D. L., Rhys, C. A., Hudson, E. K., Dianov, G. L., Hansford, R. G., and Bohr, V. A. (1997). J. Biol. Chem. 272, 27338-27344.
Cutler, R. G. (1991). Amer. J. Clin. Nutr. 53, 373S-379S.
Davies, J. A., Quintanilha, A. T., Brooks, G. A., and Packer, L. (1982). Biochem. Biophys. Res. Commun. 107, 1198-1205.
Domena, J. D., Timmer, R. T., Dicharry, S. A., and Mosbaugh, D. W. (1988). Biochemistry 27, 6742-6751.
Dutton, P. L., Moser, C. C., Sled, V. D., Daldal, F., and Ohnishi, T. (1998). Biochim. Biophys. Acta 1364, 245-257.
Fleming, J. E., Leon, H. A., and Miquel, J. (1981). Exp. Gerontol. 16, 287-293.
Floyd, R. A., Zaleska, M. M., and Harmon, H. J. (1984). In Free Radicals in Molecular Biology, Aging and Disease (Aarmstrong, D., ed.), Raven Press, New York, pp. 143-161.
Forman, H. J., and Azzi, A. (1997). FASEB J. 11, 374-375.
Funakaga, M. and Yielding, K. L. (1979). Biochem. Biophys. Res. Commun. 90, 582-586.
García de la Asunción, J., Millan, A., Pla, R., Bruseghini, L., Esteras, A., Pallardo, F. V., Sastre, J., and Viña, J. (1996). FASEB J. 10, 333-338.
Gaziano, J. M., and Hennekens, C. H. (1995). Cont. Internal Med. 7, 9-14.
Gey, K. F., Puska, P., Jordan, P., Moser, U. K. (1991). Amer. J. Clin. Nutr. 53, 326-334.
Goodrick, C. L. (1980). Gerontology 26, 22-33.
Grigorieff, N. (1998). J. Mol. Evol. 277, 1033-1046.
Guarnieri, C. C., Muscari, C., and Caldarera, C. M. (1992). In Free Radicals and Aging (Emerit, E. and Chance, B., eds.), Birkhäuser, Basel, pp. 73-77.
Hansford, R. G., Hogue, B. A., and Mildaziene, V. (1997). J. Bioenerg. Biomembr. 29, 89-95.
Harman, D. (1956). J. Gerontol. 11, 298-300.
Harman, D. (1972). J. Amer. Geriatr. Soc. 20, 145-157.
Herrero, A. and Barja, G. (1997a). Mechan. Ageing Develop. 98, 95-111.
Herrero, A., and Barja, G. (1997b). J. Bioenerg. Biomembr. 29, 241-249.
Herrero, A. and Barja, G. (1998). Mechan. Ageing Develop. 103, 133-146.
Hiraku, Y. and Kawanishi, S. (1996). Cancer Res. 56, 5172-5178.
Hinkle, P. C., Butow, R. A., Racker, E., and Chance, B. (1967). J. Biol. Chem. 242, 5169-5173.
Holloszy, J. O. (1997). J. Appl. Physiol. 82, 399-403.
Holloszy, J. O., Smith, E. K., Vining, M., and Adams, S. A. (1985). J. Appl. Physiol. 59, 826-831.
Jackson, M. J., Edwards, R. H. T., and Symons, M. C. R. (1985). Biochim. Biophys. Acta 847, 185-190.
Kwong, L. K., and Sohal, R. (1998). Arch. Biochem. Biophys. 350, 118-126.
Ku, H. H., and Sohal, R. S. (1993). Mechan. Ageing Develop. 72, 67-76.
Ku, H. H., Brunk, UT, and Sohal, R. S. (1993). Free Radical Biol. Med. 15, 621-627.
Lai C. K., and Clark, J. B. (1979). Methods Enzymol. 55, 51-60.
Lee, I. M., Sieh, C. C. H., and Paffenbarger, R. S. (1995). J. Amer. Med. Assoc. 273, 1179-1184.
Lee, Y. S., Coi, J. Y., Park, M. K., Choi, E. M., Kasai, H., and Chung, M. H. (1996). Mutat. Res. 364, 227-233.
Loft, S., Deng, X., Tuo, J., Wellejus, A., Sorensen, M., and Poulsen, H. E. (1999). Free Radical Res., 29, 525-539.
López-Torres, M., Pérez-Campo, R., Rojas, C., Cadenas, S., and Barja, G. (1993a). Mechan. Ageing Develop. 70, 177-179.
López-Torres, M., Pérez-Campo, R., Rojas, C., Cadenas, S., and Barja de Quiroga, G. (1993b). Free Radical. Biol. Med. 15, 133-142.
López-Torres M., Pérez-Campo, R., Fernández, A., Barba, C., and Barja de Quiroga, G. (1993c). J. Neurosci. Res, 34, 233-242.
Loschen, G., Flohé, L., and Chance, B. (1971). FEBS Lett. 18, 261-264.
Loschen, G., Azzi, A., and Flohé, L. (1973). FEBS Lett. 33, 84-88.
Loschen, G., Azzi, A., Richter, C., and Flohé, L. (1974). FEBS Lett. 42, 68-72.
Matsuno-Yagi, A., and Hatefi, Y (1996). J. Biol. Chem. 271, 6164-6171.
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.
Myers, K.A., Saffhill, R., and O'Connor, P.J. (1988). Carcinogenesis 9, 285-292.
Miquel, J. (1991). Arch. Gerontol. Geriatr. 12, 99-117.
Muscari, C., Frascaro, M., Guarnieri, C., and Caldarera, C.M. (1990). Biochim. Biophys. Acta 1015, 200-204.
Nohl, H. (1986) In Modern Aging Research. Free Radicals, Aging and Degenerative Diseases (Johnson, J. E., Walford, R., and Harman, D. eds.), Vol. 8. Alan Liss, New York, pp.77-97.
Nohl, H. (1987). FEBS Lett. 214, 269-273.
Nohl, H. and Jordan, W. (1986). Biochem. Biophys. Res. Commun. 138, 533-539.
Nohl, H., and Hegner, D. (1978). Eur. J. Biochem. 82, 563-567.
Nohl, H. and Stolze, K. (1992). Free Radical Res. Commun. 16, 409-419.
Nohl, H., Staniek, K., and Gille, L. (1997). Exp. Gerontol. 32, 485-500.
Ogburn, C. E., Austad, S. N., Holmes, D. J., Kiklevich, J. V., Gollahon, K., Rabinovitch, P. S., and Martin, G,M. (1998). J. Gerontol. 53, B287-B292.
Orr, W. C., and Sohal, R. S. (1994). Science 263, 1128-1130.
Ozawa, T. (1995). Exp. Gerontol. 30, 269-290.
Paffenbarger, R. S., Hyde, R. T., Wing, A. L., and Hsie, C. (1986). New Engl. J. Med. 314, 605-613.
Pamplona, R., Prat, J., Cadenas, S., Rojas, C., Pérez-Campo, R., López-Torres, M., and Barja, G. (1996). Mechan. Ageing Develop. 86, 53-66.
Pamplona, R., Portero-Otín, M., Ruiz, C., Prat, J., Bellmunt, M. J., and Barja G. (1998). J. Lipid Res. 39, 1989-1994.
Pamplona, R., Portero-Otín, M., Requena, J. R., Thorpe, S. R., Herrero, A.,and Barja, G. (1999a). Mechan. Ageing Develop., 106, 283-296.
Pamplona, R., Portero-Otín, M., Riba, D., Ledo, F., Gredilla, R., Herrero, A., and Barja, G.(1999b). Aging Clin. Exp. Res, 11, 44-49.
Pearl, R. (1928). The Rate of Living, University of London Press, London.
Pérez-Campo, R., López-Torres, M., Rojas, C., Cadenas, S., and G. Barja (1994). J. Comp. Physiol. 163, 682-689.
Pérez-Campo, R., López-Torres, M., Cadenas, S., Rojas, C., and G. Barja (1998). J. Comp. Physiol. 168, 149-158.
Pitkänen, S. and Robinson, B. H. (1996). J. Clin. Invest. 98, 345-351.
Priemé, H., Loft, S., Nyyssönen, K., Salonen, J. T., and Poulsen, H. E. (1997). Amer. J. Clin. Nutr. 65, 503-507.
Prinzinger, R. (1993). Comp. Biochem. Physiol. 105A, 609-615.
Ragan, C. I. (1987). Current Topics Bioenerg. 15, 1-36.
Reznick, A., and Gershon, D. (1999). In Methods in Aging Research (Yu, B. P. ed.), CRC Press, Boca Raton, Florida, pp. 167-190.
Richter, C. (1995). Current Topics Bioenerg. 17, 1-19.
Richter, C., Park, J. W., and Ames, B. N. (1988). Proc. Natl. Acad. Sci. U.S. 85, 6465-6467.
Robinson, B. H. (1998). Biochim. Biophys. Acta 1364, 271-286.
Rubner, M. (1908). Das Problem der Lebensdauer und seine Beziehungen zu Wachstum und Ernährung (R. Oldenburg, ed.), München.
Saul, R. L., Gee, P., and Ames, B. N. (1987). In Modern Biological Theories of Aging (Warner, H. R. ed.), Raven Press, New York, pp. 113-129.
Sawada, M. and Carlsson, J. C. (1987). Mechan. Ageing Develop. 41, 125-137.
Schmidt-Nielsen, K. (1984). Scaling. Why Is Animal Size so Important?, Cambridge Univ. Press, New York, pp. 106-108.
Sherratt, H. S. A., Watmough, N. J., Johnson, M. A., and Turnbull, D. M. (1988). Methods Biochem. Anal. 33, 304-305.
Sohal, R. S. and Weindruch, R. (1996). Science 273, 59-63.
Sohal, R. S., Svensson, I., Sohal, B. H., and Brunk, U. T. (1989). Mechan. Ageing Develop. 49, 129-135.
Sohal, R. S., Svensson, I., and Brunk, U. T. (1990). Mechan. Ageing Develop. 53, 209-215.
Sohal, R. S., Ku, H. H., and Agarwal, S. (1993). Biochem. Biophys. Res. Commun. 196, 7-11.
Sohal, R. S., Ku, H. H., Agarwal, S., Forster, M. J., and Lal, H. (1994). Mechan. Ageing Develop. 74, 121-133.
Sohal, R. S., Agarwal, S., and Sohal, B. H. (1995a). Mechan. Ageing Develop. 81, 15-25.
Sohal, R. S., Sohal, B. H., and Orr, W. C. (1995b). Free Radical Biol. Med. 19, 499-509.
Sorgato, M. C., Sartorelli, L., Loschen, G., and Azzi, A. (1974). FEBS Lett. 45, 92-95.
Souza-Pinto, N. C., Croteau, D. L., Hudson, E. K., Hansford, E. K., and Bohr, R. G. (1998). Revista de Farmacia e Bioquímica da Universidade de Sao Paulo, vol. 34, Presented at the 16-04 Symposium of the IX Biennial Meeting of the International Society for Free Radical Research, Sao Paulo, 7–11 September, 1998, pp. 73.
Takeshigue, K., and Minakami, S. (1979). Biochem. J. 180, 129-135.
Thyagarajan, B., Padua, R. A., and Campbell, C. (1996). J. Biol. Chem. 271, 27536-27543.
Tolmasoff, J. M., Ono, T., and Cutler, R. G. (1980). Proc. Natl. Acad. Sci U.S. 77, 2777-2781.
Tomkinson, A. E., Bonk, R. T., and Linn, S. (1988). J. Biol Chem. 263, 12532-12537.
Tomkinson, A. E., Bonk, R. T., Kim, J., Bartfeld, N., and Linn, S. (1990). Nucleic Acid Res. 18, 929-935.
Turrens, J. F. (1997). Biosci. Rep. 17, 3-8.
Turrens, J. F., and Boveris, A. (1980). Biochem. J. 191, 421-427.
Turrens, J. F., Alexandre, A., and Lehninger, A. L. (1985). Arch. Biochem. Biophys. 237, 408-414.
Tyler, D. D. (1992). The Mitochondria in Health and Disease, VCH, New York, pp. 90, 172–188, 253, and 305–310.
Tzagoloff, A. (1982). Mitochondria, Plenum Press, New York, pp. 136-137, 140–141.
Von Jagow, G., and Engel, W. D. (1981). FEBS Lett. 136, 19-24.
Williams, J. N. (1968). Biochim. Biophys. Acta 162, 175-181.
Yu, B. P. (1995). In Handbook of Physiology, Section 11: Aging (Masoro, E. J., ed.), Oxford University Press, New York, 613-631.
Zastawny, T. H., Czerwinska, B., Drzewiecka, B., and Olinski, R. (1997). Free Radical Biol. Med. 22, 101-107.
Zhan, H., Sun, C. P., Liu, C. G., and Zhou, J. H. (1992). Mechan. Ageing Develop. 62, 111-116.
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Barja, G. Mitochondrial Oxygen Radical Generation and Leak: Sites of Production in States 4 and 3, Organ Specificity, and Relation to Aging and Longevity. J Bioenerg Biomembr 31, 347–366 (1999). https://doi.org/10.1023/A:1005427919188
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DOI: https://doi.org/10.1023/A:1005427919188