Bacterial Mutants Resistant to Uncouplers

Abstract

Evidence from many laboratories over the last twenty years has firmly established the central role of proton translocation in energy transduction. The tenets of Peter Mitchell’s^lchemiosmotic theory are now almost universally accepted. The energization of solute transport, flagellar motion and oxidative phosphorylation in bacteria have been explained in chemiosmotic terms. The first requisite of the chemiosmotic theory is that the cell membrane must not be highly permeable to protons. Such relative impermeability permits the establishment of a protonmotive force due to the unequal distribution of protons on either side of the membrane. It is the tendency of protons to flow down their electrochemical gradient through specialized channels, such as the F₀ of BF₁F₀ ATPase or proton-solute symporters, that drives ATP syn-thesis or solute uptake. Among the substantial evidence that proton translocation is essential to energy transduction is the effect of uncouplers of oxidative phosphorylation on membrane proton permeability.^2,3 Acting as weak acids, classic uncouplers such as dinitrophenol and carbonylcyanide mchlorophenylhydrazone (CCCP) have been shown to dissipate the protonmotive force by permeabilizing membranes to protons. On the other hand, there have also been reports of uncoupler-binding entities within energy transducing membranes. ^4–6