Detrimental Effects of Methyl Hydroperoxy-Epoxy-Octadecenoate on Mitochondrial Respiration: Detoxication by Rat Liver Mitochondria1

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Abstract
1. Methyl hydroperoxy-epoxy-octadecenoate (ML-X) inhibited state 3 respiration of rat heart and liver mitochondria with glutamate and malate as substrates. It also inhibited the NADH oxidase and NADH-ubiquinone-1 reductase activities of rat heart and liver submitochondrial particles (SMP). 2. In liver mitochondria and SMP, these inhibitory effects of ML-X were transient, whereas in heart mitochondria and SMP, recovery of the respiratory activities did not occur. 3. Results from high pressure liquid chromatography and 13C-NMR studies indicated that ML-X was converted to hydroperoxy-epoxy-octadecenoic acid (L-X) by incubation with liver mitochondria or SMP but not with heart mitochondria. 4. Purified L-X apparently inhibited state 3 respiration of heart and liver mitochondria with glutamate and malate as substrates, but the amount required for 50% inhibition was 2–3 times larger than that of ML-X. 5. Heart mitochondria adsorbed 36% of the added ML-X, while only 10% of the added L-X was adsorbed. 6. These findings suggest that the recovery of the ML-X-inhibited respiratory activities of liver mitochondria and SMP occurs by conversion of ML-X to L-X, which is only weakly adsorbable on the mitochondrial membrane.