Protonic conductance across phospholipid bilayer membranes induced by uncoupling agents for oxidative phosphorylation.

The chemiosmotic coupling hypothesis for oxidative phosphorylation proposed by Mitchell1 postulates that electron transport along the respiratory chain in the mitochondrial membrane generates a transmembrane pH gradient, which becomes the immediate driving force for the enzymatic synthesis of adenosine 5'-triphosphate (ATP) from adenosine 5'-diphosphate (ADP) and phosphate through the reverse action of a vectorial ATPase system in the membrane. Mitchell has proposed that uncoupling agents such as 2,4-dinitrophenol, which uncouple phosphorylation of ADP from electron transport, are not inhibitors of specific enzymatic reactions per se, but act as lipid-soluble proton donor-acceptor systems that dissolve in the lipid phase of the membrane and conduct protons across it, thus preventing formation of pH gradients during electron transport. Experimental evidence for and against the Mitchell hypothesis has been discussed.