Organizational changes in phospholipid multibilayers induced by uncouplers of oxidative phosphorylation: A spin label study

Abstract

A cholestane spin probe was used to study the effect of uncouplers of oxidative phosphorylation (2,4-dinitrophenol, pentachlorophenol and dicumarol) on the degree of organization of phospholipids in hydrated multibilayers. Disruptive effects were observed—their magnitude depending on pH, time and the presence of cholesterol. A correlation between changes in probe organization and ion conductivity, with maximum effects at the pH corresponding to the p K of the uncoupler, could be demonstrated in the films containing cholesterol. Egg lecithin films containing no cholesterol were disordered maximally at pH 4.0 irrespective of the uncoupler used. The effect of uncouplers on the probe disorganization varied with time after exposure. These time effects indicated that relative movement of uncoupler, probe and lipid molecules occur to produce lipid organizations differing from those after initial exposure to uncoupler. The results show that even in a simple model system uncoupler effects may be complex, and suggest that changes in bilayer lipid organization parameters may play a role in uncoupling oxidative phosphorylation.