On the Mechanism of Transport by the Uncoupling Protein from Brown Adipose Tissue Mitochondria

  • Eduardo Rial
  • David G. Nicholls


The uncoupling protein enables brown adipose tissue mitochondria to uncouple respiration from ATP synthesis under thermogenic conditions by catalyzing re-entry of protons extruded by the respiratory chain. Two ligands, purine nucleotides and fatty acids, interact specifically with the protein to modulate its transport activity (for review see Rial & Nicholls, 1987).


Brown Adipose Tissue Proton Conductance Uncouple Protein Brown Adipocyte Purine Nucleotide 
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  1. Aquila H, Link TA, Klingenberg M (1985) The uncoupling protein from brown fat is related to the mitochondrial ADP/ATP carrier. Analysis of sequence homologies and of folding of the protein in the membrane. EMBO J 4:2369–2376PubMedGoogle Scholar
  2. Aquila H, Link TA, Klingenberg M (1987) Solute carriers involved in energy transfer of mitochondria form a homologous protein family. FEBS Lett 212:1–9PubMedCrossRefGoogle Scholar
  3. Cannon B, Nicholls DG, Lindbere O (1973) Purine nucleotides and fatty acids in energy coupling in mitochondria from brown adipose tissue. In: Azzone GF, Ernster L, Papa S, Quagliariello E, Siliprandi N (eds) Mechanisms in Bioenergetics. Academic Press, New York, pp 357–363Google Scholar
  4. Cunningham SA, Wiesinger H, Nicholls DG (1986) Quantification of fatty acid activation of the uncoupling protein in brown adipocytes and mitochondria from the guinea pig. Eur J Biochem 157:415–420PubMedCrossRefGoogle Scholar
  5. Fernández M, Nicholls DG, Rial E (1987) The uncoupling protein from brown-adiposetissue mitochondria: chymotrypsin-induced structural and functional modifications. Eur J Biochem 164:675–680PubMedCrossRefGoogle Scholar
  6. Heaton GM, Wagenvoord RJ, Kemp A, Nicholls DG (1978) Brown adipose tissue mitochondria: photoaffinity labelling of the regulatory site for energy dissipation. Eur J Biochem 82:515–521PubMedCrossRefGoogle Scholar
  7. Klingenberg M (1985) Principles of carrier catalysis elucidated by comparing two similar membrane translocators from mitochondria, the ADP/ATP carrier and the uncoupling protein. Ann New York Acad Sci 456:279–288CrossRefGoogle Scholar
  8. Klingenberg M (1988) Nucleotide binding to uncoupling protein: Mechanism of control by protonation. Biochemistry 27:781–791PubMedCrossRefGoogle Scholar
  9. Klingenberg M, Winkler E (1985) The reconstituted isolated uncoupling protein is a membrane potential driven H+ translocator. EMBO J 4:3087–3092PubMedGoogle Scholar
  10. Kopecky J, Guerrieri F, Jezek P, Drahota Z, Houstek J (1984) Molecular mechanism of uncoupling in brown adipose tissue mitochondria: the nonidentity of proton and chloride conducting pathways. FEBS Lett 170:186–190PubMedCrossRefGoogle Scholar
  11. Kopecky J, Jezek P, Drahota Z, Houstek J (1987) Control of uncoupling protein in brown-fat mitochondria by purine nucleotides: chemical modification by diazobenzenesulfonate. Eur J Biochem 164:687–694PubMedCrossRefGoogle Scholar
  12. LaNoue KF, Koch CD, Meditz RB (1982) Mechanism of action of norepinephrine in hamster brown adipocytes. J Biol Chem 257:13740–13748PubMedGoogle Scholar
  13. LaNoue KF, Strzelecki T, Strzelecka D, Koch C (1986) Regulation of the uncoupling protein in brown adipose tissue. J Biol Chem 261:298–305PubMedGoogle Scholar
  14. Locke RM, Rial E, Nicholls DG (1982a) The acute regulation of proton conductance in cell and mitochondria from the brown fat of cold-and warm-adapted guineapigs. Eur J Biochem 129:381–387PubMedCrossRefGoogle Scholar
  15. Locke RM, Rial E, Scott ID, Nicholls DG (1982b) Fatty acids as acute regulators of the proton conductance of hamster brown fat mitochondria. Eur J Biochem 129:373–380PubMedCrossRefGoogle Scholar
  16. Nicholls DG (1974) Hamster brown adipose tissue mitochondria: the chloride permeability of the inner membrane under respiring conditions, the influence of purine nucleotides. Eur J Biochem 49:585–593PubMedCrossRefGoogle Scholar
  17. Nicholls DG (1976) Hamster brown adipose tissue mitochondria: purine nucleotide control of the ion conductance of the inner membrane, the nature of the nucleotide site. Eur J Biochem 62:223–228PubMedCrossRefGoogle Scholar
  18. Nicholls DG (1977) The effective proton conductance of the inner membrane of mitochondria from brown adipose tissue: dependence on proton electrochemical gradient. Eur J Biochem 77:349–356PubMedCrossRefGoogle Scholar
  19. Nicholls DG (1979) Brown adipose tissue mitochondria. Biochim Biophys Acta 549:1–29PubMedGoogle Scholar
  20. Nicholls DG, Lindberg O (1973) Brown adipose tissue mitochondria: the influence of albumin and nucleotides on passive ion permeabilities. Eur J Biochem 37:523–530PubMedCrossRefGoogle Scholar
  21. Nicholls DG, Heaton G (1978) Anion uniport across the inner membrane of brown adipose tissue mitochondria. In: Azzone GF, Avron M, Metcalfe JC, Quagliariello E, Siliprandi N (eds) The Proton and Calcium Pumps. Elsevier, Amsterdam, pp 309–318Google Scholar
  22. Rafael J, Ludolph HJ, Hohorst HJ (1969) Mitochondria from brown adipose tissue: uncoupling of oxidative phosphorylation by long chain fatty acids and recoupling by guanosine triphosphate. Hoppe-Seyler’s Z Physiol Chem 350:1121–1131PubMedCrossRefGoogle Scholar
  23. Rial E, Nicholls DG (1984) The mitochondrial uncoupling protein from guinea-pig brown adipose tissue: synchronous increase in structural and functional parameters during cold-adaptation. Biochem J 222:685–693PubMedGoogle Scholar
  24. Rial E, Nicholls DG (1986) Chemical modification of the brown-fat-mitochondrial uncoupling protein with tetranitromethane and N-ethylmaleimide: a cysteine residue is implicated in the nucleotide regulation of anion permeability. Eur J Biochem 161:689–694PubMedCrossRefGoogle Scholar
  25. Rial E, Nicholls DG (1987) The uncoupling protein from brown adipose tissue mitochondria. Cell Biol Rev 11:75–104Google Scholar
  26. Rial E, Poustie A, Nicholls DG (1983) Brown adipose tissue mitochondria: the regulation of the 32,000 Mr uncoupling protein by fatty acids and purine nucleotides. Eur J Biochem 137:197–203PubMedCrossRefGoogle Scholar
  27. Runswick MJ, Powell SJ, Nyren P, Walker JE (1987) Sequence of the bovine mitochondrial phosphate carrier: structural relationship to ADP/ATP translocase and the brown fat mitochondrial uncoupling protein. EMBO J 6:1367–1373PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • Eduardo Rial
    • 1
  • David G. Nicholls
    • 1
  1. 1.Department of Biochemistry, Medical Sciences InstituteUniversity of DundeeDundeeScotland, UK

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