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The chemical energy of nutrient molecules is converted in to ATP during the process of oxidative phosphorylation in mitochondria. Since the electrochemical potential gradient of H+ formed across the inner mitochondrial membrane by the oxidation of respiratory substrates is utilized as a driving force for ATP synthesis, the mitochondrial inner membrane is highly impermeable to H+. An increase in the permeability of this membrane to H+ causes inhibition of ATP synthesis, and chemicals that cause such an increase are called uncouplers. Ordinary known uncouplers are hydrophobic weak acids and show their activity by acting as protonophores. On the contrary, in recent studies, a variety of chemicals were found to act as uncouplers, not by acting as a protonophore, but by inducing permeability transition of the inner mitochondrial membrane or by inducing molecular “slippage” of the primary H+ pump. In this review article, recent progress made from studies on the uncouplers of oxidative phosphorylation is presented and discussed.

Recent Progress in Studies on The Uncouplers of Oxidative Phosphorylation.