New insights into mechanisms of anion uniport through the uncoupling protein of brown adipose tissue mitochondria.
GDP-sensitive Cl- uniport is a widely studied property of the uncoupling protein of brown adipose tissue mitochondria; nevertheless, little is known about its mechanism and there is even controversy over whether this protein transports Cl-. Using a fluorescent probe assay, we have demonstrated non-ohmic, electrophoretic, GDP-sensitive Cl- uniport into proteoliposomes reconstituted with purified uncoupler protein. We have also identified a large number of new anionic substrates for this porter that also inhibit Cl- uniport competitively. Anion transport, its inhibition by GDP and anion inhibition of Cl- uniport are all strongly dependent on anion hydrophobicity. These surprising results are consequential for hypotheses of common transport mechanisms in the gene family of mitochondrial anion porters.
Department of Pharmacology, Medical College of Ohio, Toledo 43699-0008.
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D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D006224:Cricetinae; D005456:Fluorescent Dyes; D006153:Guanosine Diphosphate / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D008647:Mesocricetus; D008928:Mitochondria / Q000378:metabolism*; D011806:Quinolinium Compounds
D002352:Carrier Proteins; D002712:Chlorides; D005456:Fluorescent Dyes; D007473:Ion Channels; D011806:Quinolinium Compounds; D006153:Guanosine Diphosphate; C052335:6-methoxy-N-(3-sulfopropyl)quinolinium