The Uncoupling of Oxidative Phosphorylation of Mouse- Liver Mitochondria in vivo by Usnic Acid

(+) Usnic acid isolated from the local lichen species Usneaarticulata had a median lethal dose of 180 mg/kg to mice (s.c. injection).The symptoms of the toxicity exhibited by (+) usnic acid wassimilar to those of classical uncouplers of oxidative phosphorylation.Mice injected with 200 mg/kg of (+) usnic acid produced significantuncoupling of isolated hepatic mitochondria. The signs of uncouplingincluded: release of respiratory control, inhibition of respiration (80%in the presence of ADP and 60% in its absence), hindering of ATP biosynthesis,and stimulation of Mg+2-ATPase activity (two-fold increase).In this respect, (+) usnic acid, a lipophilic weak acid with twoionizable hydrogens, acts in a similar fashion to many protonophoricuncouplers which dissipate the proton motive force (delta mu H+)across the inner mitochondrial membrane, therefore disrupting thetight coupling mechanism between electron transport and ATP synthesis.