Vitamin E regulates mitochondrial hydrogen peroxide generation

The mitochondrial electron transport system consumes more than 85% of all o xygen used by the cells, and up to 5% of the oxygen consumed by mitochondri a is converted to superoxide, hydrogen peroxide, and other reactive oxygen species (ROS) under normal physiologic conditions. Disruption of mitochondr ial ultrastructure is one of the earliest pathologic events during vitamin E depletion. The present studies were undertaken to test whether a direct l ink exists between vitamin E and the production of hydrogen peroxide in the mitochondria. In the first experiment, mice were fed a vitamin E-deficient or-sufficient diet for 15 weeks, after which the mitochondria from liver a nd skeletal muscle were isolated to determine the rates of hydrogen peroxid e production. Deprivation of vitamin E resulted in an approximately 5-fold increase of mitochondrial hydrogen peroxide production in skeletal muscle a nd a 1-fold increase in liver when compared with the vitamin E-supplemented group. To determine whether vitamin E can dose-dependently influence the p roduction of hydrogen peroxide, four groups of male and female rats were fe d diets containing 0, 20, 200, or 2000 IU/kg vitamin E for 90 d. Results sh owed that dietary vitamin E dose-dependently attenuated hydrogen peroxide p roduction in mitochondria isolated from liver and skeletal muscle of male a nd female rats. Female rats, however, were more profoundly affected by diet ary vitamin E than male rats in the suppression of mitochondrial hydrogen p eroxide production in both organs studied. These results showed that vitami n E can directly regulate hydrogen peroxide production in mitochondria and suggest that the overproduction of mitochondrial ROS is the first event lea ding to the tissue damage observed in vitamin E-deficiency syndromes. Data further suggested that by regulating mitochondrial production of ROS, vitam in E modulates the expression and activation of signal transduction pathway s and other redox-sensitive biologic modifiers, and thereby delays or preve nts degenerative tissue changes. (C) 1999 Elsevier Science Inc.