Brown-adipose-tissue mitochondria: the regulation of the 32000-Mr uncoupling protein by fatty acids and purine nucleotides.

The increased proton permeability induced by the addition of a synthetic proton translocator to non-respiring hamster brown-fat mitochondria is unaffected by purine nucleotide addition. In contrast the permeability induced by fatty acids is inhibited by nucleotide, indicating that fatty acids act at the 32000-Mr uncoupling protein. Fatty acids lower the affinity of nucleotide binding to the 32000-Mr protein, but not sufficiently to explain their uncoupling action. The sensitivity of the fatty acid modulation of permeability is dependent on chain length, extent of unsaturation and pH. There is a requirement for an unesterified carboxyl group. In respiring mitochondria fatty acids act in the presence of nucleotide by lowering the 'break-point' potential at which the conductance of the 32000-Mr protein increases. Fatty acids have no effect on the chloride uniport activity of the 32000-Mr protein, but decouple the interference between chloride and protons when the simultaneous transport of both ions is attempted.