Methyl hydroperoxy-epoxy-octadecenoate as an autoxidation product of methyl linoleate: a new inhibitor-uncoupler of mitochondrial respiration.

A new peroxide compound (ML-X) was isolated from an autoxidation product of methyl linoleate and was determined as methyl 9-hydroperoxy-12, 13-epoxy-10-octadecenoate. This compound inhibited state 3 respiration of rat heart- and liver mitochondria when glutamate and malate were used as substrates, but not when the substrate was succinate. State 4 respiration of mitochondria was not affected when glutamate-malate was used as the substrate, but it was stimulated when the substrate was succinate. ML-X inhibited oxidative phosphorylation of the mitochondria and abolished the membrane potential formed by respiration or by added ATP. NADH oxidase activity of submitochondrial particles was inhibited by ML-X but succinate oxidase activity was not inhibited. NADH-acceptor reductase activities of submitochondrial particles were inhibited by ML-X to the same extents as by rotenone. These findings show that ML-X has dual effects on mitochondrial respiration as (1) an inhibitor of NADH dehydrogenase complex and (2) an uncoupler. Neither methyl linoleate monohydroperoxide nor methyl epoxy stearate has such effects. ML-X is a new type of inhibitor-uncoupler of mitochondrial respiration in which hydroperoxy- and epoxy groups co-operate.