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.
Garlid
K D
KD
Department of Pharmacology, Medical College of Ohio, Toledo 43699-0008.
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