Mode of Action of Uncoupler and Mechanism of Oxidative Phosphorylation.

A number of studies on the mechanism of uncoupler action appear to be incompatible with the chemiosmotic hypothesis which assumes that bulk proton electrochemical gradient (ΔμH) is the only intermediate linking between oxidation and phosphotylation in mitochondria. Decouplers such as general anesthetics seem to induce uncoupling by releasing protons from intramembrane proton pathway or inducing the proton slip of proton pumps. Uncoupling by weakly acidic uncouplers could be a mixture of the collapse of ΔμH and the decoupling (or proton sliping).