On the nature of the uncoupling effect of fatty acids

The effect of palmitic acid on the electrical potential differences delta psi across the inner mitochondrial membrane appears to depend on the medium in which mitochondria are incubated. In medium A (cf. Luvisetto et al. (1987), Biochemistry, 26, 7332-7338) delta psi decreases much more than in medium B (cf. Rottenberg and Hashimoto (1986), Biochemistry, 25, 1747-1755) at concentrations of fatty acid which equally stimulate the rate of respiration in state 4. Valinomycin and NaCl were both present in medium B and absent in medium A. However, in both media the pattern of the P/O ratio as a function of antimycin in the presence of a constant amount of palmitic acid or of FCCP shows similar behaviour. We conclude that in both media palmitic acid increases the membrane conductance to protons, but for unclear reasons the delta psi assay fails to measure the decline of delta psi in medium B. However, the increase in membrane conductance induced by palmitic acid does not quantitatively account for the stimulation of the rate of respiration.