THE ROLE OF REACTIVE OXYGEN SPECIES IN MITOCHONDRIAL PERMEABILITY TRANSITION

We have provided evidence that mitochondrial membrane permeability tra nsition induced by inorganic phosphate, uncouplers or prooxidants such as t-butyl hydroperoxide and diamide is caused by a Ca2+-stimulated p roduction of reactive oxygen species (ROS) by the respiratory chain, a t the level of the coenzyme Q. The ROS attack to membrane protein thio ls produces cross-linkage reactions, that may open membrane pores upon Ca2+ binding. Studies with submitochondrial particles have demonstrat ed that the binding of Ca2+ to these particles (possibly to cardiolipi n) induces lipid lateral phase separation detected by electron paramag netic resonance experiments exploying stearic acids spin labels. This condition leads to a disorganization of respiratory chain components, favoring ROS production and consequent protein and lipid oxidation.