The uncoupling of oxidative phosphorylation of mouse-liver mitochondria in vivo by usnic acid

Abstract EN

(+) Usnic acid isolated from the local lichen species Usnea articulata had a median lethal dose of 180 mg/kg to mice (s.c.

injection).

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 biosynthesis, and stimulation of Mg +2-ATPase activity (two-fold increase).

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 synthesis.