Role of Mitochondria in Oxidative Stress and Aging

作者：Giorgio Lenaz, Carla Bovina, Marilena D’Aurelio, Romana Fato, Gabriella Formiggini, Maria Luisa Genova, Giovanni Antonio Giuliano, Milena Merlo Pich, Ugo Paolucci, Giovanna Parenti Castelli, Barbara Ventura · 发表于：Annals of the New York Academy of Sciences · 年份：2002 · DOI：10.1111/j.1749-6632.2002.tb02094.x · 被引用次数：492 · 研究领域：Coenzyme Q10 studies and effects、Mitochondrial Function and Pathology、Biochemical Acid Research Studies

The mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS), considered as the pathogenic agent of many diseases and of aging. We have investigated the role of Complex I in superoxide radical production and found by combined use of specific inhibitors of Complex I that the one-electron donor in the Complex to oxygen is a redox center located prior to the sites where three different types of coenzyme Q (CoQ) competitors bind, to be identified with an Fe-S cluster, most probably N2, or possibly an ubisemiquinone intermediate insensitive to all the above inhibitors. Short-chain coenzyme Q analogues enhance superoxide formation, presumably by mediating electron transfer from N2 to oxygen. The clinically used CoQ analogue idebenone is particularly effective, raising doubts about its safety as a drug. The mitochondrial theory of aging considers somatic mutations of mitochondrial DNA induced by ROS as the primary cause of energy decline; in rat liver mitochondria, Complex I appears to be most affected by aging and to become strongly rate limiting for electron transfer. Mitochondrial energetics is also deranged in human platelets upon aging, as demonstrated by the decreased Pasteur effect (enhancement of lactate production by respiratory inhibitors). Cells counteract oxidative stress by antioxidants: CoQ is the only lipophilic antioxidant to be biosynthesized. Exogenous CoQ, however, protects cells from oxidative stress by conversion into its reduced ant...