Uncoupling effect of fungal hydroxyanthraquinones on mitochondrial oxidative phosphorylation

Abstract

Structure-uncoupling activity relationship of seven anthraquinone derivatives were investigated using rat liver mitochondria. Three compounds bearing the free hydroxyl group at the β-position of their anthraquinone nucleus (1,3,6,8-tetrahydroxyanthraquinone, 1-acetyl-2,4,5,7-tetrahydroxy-9,10-anthracenedione and skyrin) exhibited uncoupling effect. Rugulosin, rugulin and physcion (all lacking the hydroxyl at the β-position) were ineffective. Erythroglaucin, a derivative of physcion with the free hydroxyl group at the γ-position, exhibited the highest uncoupling activity in the series tested. In addition, erythroglaucin abolished the energy dependent Ca2+ retention in mitochondria and induced Ca2+ leak. It also prevented the energization of mitochondrial membrane by ATP and induced a loss of the ATP induced membrane potential similarly as did carbonylcyanamide-3-chlorophenyl hydrazone (CCCP). The data show that the free hydroxyl group at either the γ-position or the β-position of anthraquinone nucleus is a prerequisite of the uncoupling activity of hydroxyanthraquinones. © 1987.