Mitochondrial free radical generation, oxidative stress, and aging

Mitochondria have been described as "the powerhouses of the cell" because t hey link the energy-releasing activities of electron transport and proton p umping with the energy conserving process of oxidative phosphorylation, to harness the value of foods in the form of ATP. Such energetic processes are not without dangers, however, and the electron transport chain has proved to be somewhat "leaky." Such side reactions of the mitochondrial electron t ransport chain with molecular oxygen directly generate the superoxide anion radical(O-2(.-)), which dismutates to form hydrogen peroxide (H2O2), which can further react to form the hydroxyl radical (HO.). In addition to these toxic electron transport chain reactions of the inner mitochondrial membra ne. the mitochondrial outer membrane enzyme monoamine oxidase catalyzes the oxidative deamination of biogenic amines and is a quantitatively large sou rce of H2O2 that contributes to an increase in the steady state concentrati ons of reactive species within both the mitochondrial matrix and cytosol. I n this article we review the mitochondrial rates of production and steady s tate levels of these reactive oxygen species. Reactive oxygen species gener ated by mitochondria, or from other sites within or outside the cell, cause damage to mitochondrial components and initiate degradative processes. Suc h toxic reactions contribute significantly to the aging process and form th e central dogma of "The Free Radical Theory of Aging." In this article we r eview current understandings of mitochondrial DNA, RNA, and protein modific ations by oxidative stress and the enzymatic removal of oxidatively damaged products by nucleases and proteases. The possible contributions of mitocho ndrial oxidative polynucleotide and protein turnover to apoptosis and aging are explored. (C) 2000 Elsevier Science Inc.