Role of -Tocopherol in the Regulation of Mitochondrial Membrane Permeability Transition

Although information about the mechanism of apoptosis is rapidly increasing, critical roles of mitochondria in the regulation of cell death remain to be elucidated. Recent studies revealed that reactive oxygen species (ROS) in cells increase prior to the onset of DNA fragmentation, a late phase event in apoptosis. An overload of Ca 2 induces a classic type of membrane permeability transition (CMPT) characterized by depolarization and swelling of mitochondria thereby releasing cytochrome c by a cyclosporin A-sensitive mechanism. In contrast, some agents induce apoptosis by increasing mitochondrial membrane permeability and swelling by some cyclosporin Aand Ca 2 -insensitive mechanism; this phenomenon is defined as non-classic type of MPT (NCMPT). However, the role of ROS and antioxidants, such as -tocopherol, in the mechanism of CMPT and NCMPT induction remains unclear. The present work overviews the role of ROS and -tocopherol in the induction of CMPT and NCMPT.