THE THIOL-SPECIFIC ANTIOXIDANT ENZYME PREVENTS MITOCHONDRIAL PERMEABILITY TRANSITION - EVIDENCE FOR THE PARTICIPATION OF REACTIVE OXYGEN SPECIES IN THIS MECHANISM

Mitochondrial swelling and membrane protein thiol oxidation associated with mitochondrial permeability transition induced by Ca2+ and inorga nic phosphate are inhibited in a dose-dependent manner either by catal ase, the thiol-specific antioxidant enzyme (TSA), a protein recently d emonstrated to present thiol peroxidase activity, or ebselen, a seleni um-containing heterocycle which also possesses thiol peroxidase activi ty. This inhibition of mitochondrial permeability transition is due to the removal of mitochondrial-generated H2O2, which can easily diffuse to the extramitochondrial space. Whereas ebselen required the presenc e of reduced glutathione as a reductant to grant its protective effect , TSA was fully reduced by mitochondrial components. Decrease in the o xygen concentration of the reaction medium also inhibits mitochondrial permeabilization and membrane protein thioloxidation, in a concentrat ion-dependent manner. The results presented in this report confirm tha t mitochondrial permeability transition induced by Ca2+ and inorganic phosphate is reactive oxygen species-dependent. The possible importanc e of TSA as an intracellular antioxidant, avoiding the onset of mitoch ondrial permeability transition, is discussed in the text.