Mitochondrial oxidative damage promoted by a synergism betweem Ca2+ and prooxidants: inner membrane permeabilization and mtDNA breakage

RESUMO

Oxidative damage of mitochondria induced by a synergism between Ca2+ and prooxidants is mediated by the attack of mitochondria-generated reactive oxygen species to membrane proteins, lipids and DNA. This results in mitochondrial DNA fragmentation, lipid peroxidation and oxidation of vicinal protein thiols producing high molecular weight membrane protein aggregates. The membrane protein alterations lead to a condition called mitochondrial membrane permeability transition, characterized by formation of nonspecific membrane protein pores sensitive to cyclosporin A, EGTA, dithiothreitol, Mg2+ and ADP. We propose that these alterations are related to the mechanisms by which cells are killed by a series of toxins, xenobiotics or pathological conditions such as prolonged hypoxia or ischemia/reperfusion.