Brown‐adipose‐tissue mitochondria: the regulation of the 32 000‐Mr uncoupling protein by fatty acids and purine nucleotides

Abstract

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-M_r uncoupling protein. Fatty acids lower the affinity of nucleotide binding to the 32000-M_r 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-M_r protein increases. Fatty acids have no effect on the chloride uniport activity of the 32000-M_r protein, but decouple the interference between chloride and protons when the simultaneous transport of both ions is attempted.