マイコトキシンと生体膜の相互作用 キノン色素によるミトコンドリア電子伝達阻害作用を中心として

Abstract

Variety of quinone and quinoid compounds have been isolated from natural sources. Knowledges on the physiological significances of quinone production in biological systems, are, however, quite limited except those of ubiquinones and plastoquinones in the biological oxidation systems. In the present review, our brief works on the interactions of several naturally occurring, toxic quinones with respriratory chain of mitochondria were described.Flavoglaucin, a benzohydroquinone derivative from Eurotium chevalieri, exerted an uncoupling effect on oxidative phosphorylation in mitochondria. The uncoupling effect of flavoglaucin, which does not release proton at neutral pH range, was considered to be closely correlated with its strong induction of mitochondrial swelling. Flavoglaucin depressed mitochondrial respiration by directly interacting with the respiratory chain at higher concentrations than those for uncoupling activity. The site of inhibition was identified to be localized mainly at complex I and inferiorly at complex III of the respiratory chain.Xanthomegnin, a naphthoquinone pigment originally from dermatophytes Trichophyton and Microsporum, was later isolated from several species of saprophytic fungi Aspergillus and Penicillium and was shown to uncouple oxidative phosphorylation. Xanthomegnin exhibited a redox response upon NADH oxidation in submitochondrial particles and in dissolved system, in Which rotenone- and antimycin-inhibitions were no longer observed. It was concluded that xanthomegnin made an electron transport-shunt between complex I and IV in the presence of cytochrome c.Averufin, an anthraquinone mycotoxin which is a biosynthetic precursor of an extremely potent hepato-carcinogen aflatoxin B1, was found to be a strong uncoupler of oxidative phosphorylation in mitochondria. At the higher concentrations than those for uncoupling activity, averufin inhibited mitochondrial respiration directly interacting with the respiratory chain at cytochrome bc1 segment, showing a similarity to the mode of inhibition by antimycin A which is a specific inhibitor to the electron transport between cytochromes b and c1.