The Metabolic Fate of Mitochondrial Hydrogen Peroxide

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Abstract
1 Mitochondrial H2O2 formation is not in equilibrium with defence mechanisms that counteract an accumulation of H2, in rat-heart cell. 2 A model for the accumulation kinetics is proposed which is consistent with the data presented. 3 Four different pathways of H2O2 metabolism are described in rat-heart mitochondria. The major site for metabolic branching of H2O2 Via different routes was found to be the mitchondrial catalase. 4 Glutathione (GSH) peroxidase accounts for only 15% of intramitochondrial H2O2 metabolism, while catalase-mediated destruction is four times more rapid. 5 Catalase activity is limited by its structural compartmentation in the matrix, while GSH peroxidase activity was found to be dependent on the availability of free GSH. 6 Catalase was shown to protect rat-heart mitochondria from upsetting redox states of GSH and pyridine nucleotides following H2O2, decomposition by GSH peroxidase. 7 Computer simulations of experimental data Suggest the existence of a third sink for mitochondrial H2O2, possibly due to mitochondrial formation of OH′ radicals; another fraction of the H2O2 matrix pool may cross the mitochondrial membrane and accumulate in the cytosol.