Transport of anions and protons by the mitochondrial uncoupling protein and its regulation by nucleotides and fatty acids. A new look at old hypotheses

摘要: The uncoupling protein generates heat by catalyzing electrophoretic proton transport across the inner membrane of brown adipose tissue mitochondria. It also transports Cl- and other monovalent anions, both anion are inhibited purine nucleotides. Several long-standing hypotheses bear on specific aspects transport, H+ nucleotide gating mechanisms in protein. We reevaluated these mitochondria liposomes reconstituted with purified protein; GDP inhibition is strictly noncompetitive unaffected either transmembrane electrical potential or fatty acids. Km Vmax values for independent pH, arguing against a common binding site OH- ions. was acids stimulated acid removal, refuting consensus hypothesis that there no interaction between through These results support mechanism which pathway anions identical distinct from site.