Phosphatidic Acid and Cardiolipin Enhance Cytochrome c-Induced Lipid Peroxidation and Suppress Reactive Oxygen Species Production by Neutrophils

Abstract

The article is devoted to the description of molecular processes that can participate in both proapoptotic and proferroptotic reactions. Using spectrofluorimetry, it was shown that cytochrome c in the presence of phosphatidic acid or cardiolipin binds to the biological membrane approximately four times more strongly than to lecithin. As a result of this interaction, there is an increase in both cytochrome c peroxidase activity (by six and 22 times for complexes with phosphatidic acid and cardiolipin, respectively) and in lipid peroxidation (by three and 17 times for complexes with phosphatidic acid and cardiolipin, respectively). Cytochrome c-induced lipid peroxidation is observed in a narrow range of cytochrome c concentrations near 0.5 μM. In addition, a decrease in the activation and production of reactive oxygen species by peritoneal neutrophils (reduction by 40 and 60%, respectively) was demonstrated under the action of cytochrome c complexes with phosphatidic acid or with cardiolipin. It is assumed that processes occurring with an increase in the intensity of both cytochrome c peroxidase reactions and cytochrome c-induced lipid peroxidation may occur during apoptosis or ferroptosis.