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

Usnic acid isolated from the local lichen species Usnea articulata had a median lethal dose of 180 mg/kg to mice (s.c. in- jection). The symptoms of the toxicity exhibited by (+) usnic acid was similar to those of classical uncouplers of oxidative phosphorylation. Mice injected with 200 mg/kg of (+) usnic acid produced significant uncoupling of isolated hepatic mitochondria. The signs of uncoupling included: release of respiratory control, inhibition of respiration (80% in the presence of ADP and 60% in its absence), hindering of ATP bi- osynthesis, and stimulation of Mg +2 -ATPase activity (two-fold in- crease). In this respect, (+) usnic acid, a lipophilic weak acid with two ionizable hydrogens, acts in a similar fashion to many protonophoric uncouplers which dissipate the proton motive force (delta mu H+) across the inner mitochondrial membrane, therefore disrupting the tight coupling mechanism between electron transport and ATP syn- thesis.