Role of α-tocopherol in the regulation of mitochondrial permeability transition

We previously showed that Ca²⁺-induced cyclosporin A-sensitive membrane permeability transition (MPT) of mitochondria occurred with concomitant generation of reactive oxygen species (ROS) and release of cytochrome c (Free Rad. Res.38, 29-35, 2004). To elucidate the role of α-tocopherol in MPT, we investigated the effect of α-tocopherol on mitochondrial ROS generation, swelling and cytochrome c release induced by Ca²⁺ or hydroxyl radicals. Biochemical analysis revealed that α-tocopherol suppressed Ca²⁺-induced ROS generation and oxidation of critical thiol groups of mitochondrial adenine nucleotide translocase (ANT) but not swelling and cytochrome c release. Hydroxyl radicals also induced cyclosporin A-sensitive MPT of mitochondria. α-Tocopherol suppressed the hydroxyl radical-induced lipid peroxidation, swelling and cytochrome c release from mitochondria. These results indicate that α-tocopherol inhibits ROS generation, ANT oxidation, lipid peroxidation and the opening of MPT, thereby playing important roles in the prevention of oxidative cell death.