Farnesol-induced generation of reactive oxygen species dependent on mitochondrial transmembrane potential hyperpolarization mediated by F(0)F(1)-ATPase in yeast.

An isoprenoid farnesol (FOH) inhibited cellular oxygen consumption and induced mitochondrial generation of reactive oxygen species (ROS) in cells of Saccharomyces cerevisiae in correlation with hyperpolarization of the mitochondrial transmembrane potential (mtDeltaPsi). The FOH-induced events were coordinately abolished with the F(1)-ATPase inhibitor sodium azide as well as the F(0)F(1)-ATPase inhibitor oligomycin, suggesting the dependence of ROS generation on mtDeltaPsi hyperpolarization mediated by the proton pumping function of F(0)F(1)-ATPase as a result of ATP hydrolysis. The role of F(1)-ATPase activity in mtDeltaPsi hyperpolarization was supported by the intracellular depletion of ATP in FOH-treated cells and its protection with sodium azide. An indirect mechanism was suggested to exist in the regulation of F(0)F(1)-ATPase by FOH to accelerate its ATP-hydrolyzing activity.