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Journal of Bioenergetics and Biomembranes

, Volume 31, Issue 5, pp 517–524 | Cite as

Mitochondrial Proton Leak and the Uncoupling Proteins

  • Jeff A. Stuart
  • Kevin M. Brindle
  • James A. Harper
  • Martin D. Brand
Article

Abstract

An energetically significant leak of protons occurs across the mitochondrial inner membranesof eukaryotic cells. This seemingly wasteful proton leak accounts for at least 20% of thestandard metabolic rate of a rat. There is evidence that it makes a similar contribution tostandard metabolic rate in a lizard. Proton conductance of the mitochondrial inner membranecan be considered as having two components: a basal component present in all mitochondria,and an augmentative component, which may occur in tissues of mammals and perhaps ofsome other animals. The uncoupling protein of brown adipose tissue, UCP1, is a clear exampleof such an augmentative component. The newly discovered UCP1 homologs, UCP2, UCP3,and brain mitochondrial carrier protein 1 (BMCP1) may participate in the augmentativecomponent of proton leak. However, they do not appear to catalyze the basal leak, as this isobserved in mitochondria from cells which apparently lack these proteins. Whereas UCP1plays an important role in thermogenesis, the evidence that UCP2 and UCP3 do likewiseremains equivocal.

Proton leak uncoupling proteins UCP1 UCP2 UCP3 BMCP1 thermogenesis sequence homology mitochondria respiration 

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REFERENCES

  1. Altschul, S. F., Gish, W., Miller, W., Myers, E. W., and Lipman, D. J. (1990). J. Mol. Biol. 215, 403-410.Google Scholar
  2. Boss, O., Samec, S., Paoloni, G. A., Rossier, C., Dulloo, A., Seydoux, J., Muzzin, P., and Giacobino, J.P. (1997). FEBS Lett. 408, 39-42.Google Scholar
  3. Boss, O., Samec, S., Desplanches, D., Mayet, M-H., Seydoux, J., Muzzin, P., and Giacobino, J-P. (1998a). FASEB J. 12, 335-339.Google Scholar
  4. Boss, O., Samec, S., Kuhne, F., Bijlenga, P., Assimacopoulos-Jeannet, F., Seydoux, J., Giacobino, J-P., and Muzzin, P. (1998b). J. Biol. Chem. 273, 5-8.Google Scholar
  5. Boyer, B. B., Barnes, B. M., Lowell, B. B., and Grujic, D. (1998). Amer. J. Physiol. 275, R1232-R1238.Google Scholar
  6. Brand, M. D., Couture, P., Else, P. L., Withers, K. W., and Hulbert, A. J. (1991). Biochem. J. 275, 81-86.Google Scholar
  7. Brand, M. D., Brindle, K. M., Buckingham, J. A., Harper, J. A., Rolfe, D. F. S., and Stuart, J. A. (1999). Intern. J. Obesity, 23,suppl. 6, 54-511.Google Scholar
  8. Brookes, P. S., Hulbert, A. J., and Brand, M. D. (1997a). Biochim. Biophys. Acta 1330, 157-164.Google Scholar
  9. Brookes, P. S., Rolfe, D. F. S., and Brand, M. D. (1997b). J. Memb. Biol. 155, 167-174.Google Scholar
  10. Brookes, P. S., Buckingham, J. A., Tenreiro, A. M., Hulbert, A. J., and Brand, M. D. (1998). Comp. Biochem. Physiol. 119B, 325-334.Google Scholar
  11. Carretero, M. V., Torres, L., Latasa, M. U., Garcia-Trevijano, E. R., Prieto, J., Mato, J. M., and Avila, M. A. (1998). FEBS Lett. 439, 55-58.Google Scholar
  12. Clandinin, M. T., Cheema, S., Pehowich, D., and Field, C. J. (1996). Lipids 31, S13-S22.Google Scholar
  13. Fleury, C., Neverova, M., Collins, S., Raimbault, S., Champigny, O., Levi-Meyrueis, C., Bouillaud, F., Seldin, M. F., Surwit, R. S., Ricquier, D., and Warden, C. H. (1997). Nature Genet. 15, 269-272.Google Scholar
  14. Gimeno, R., Dembski, M., Weng, X., Deng, N., Shyjan, A., Gimeno, C., Iris, F., Ellis, S., Woolf, E., and Tartaglia, L. (1997). Diabetes 46, 900-906.Google Scholar
  15. Gong, D-W., He, Y., Karas, M., and Reitman, M. (1997). J. Biol. Chem. 272, 24129-24132.Google Scholar
  16. Laloi, M., Klein, M., Riesmeier, J. W., Muller-Rober, B., Fleury, C., Bouillaud, F., and Ricquier, D. (1997). Nature (London) 389, 135-136.Google Scholar
  17. Lin, B., Coughlin, S., and Pilch, P. F. (1998). Amer. J. Physiol. 275, E386-E391.Google Scholar
  18. Lowell, B. B. (1998). Curr. Biol. 8, R517-R520.Google Scholar
  19. Nicholls, D. G. (1974). Eur. J. Biochem. 50, 305-315.Google Scholar
  20. Nicholls, D. G. (1979). Biochim. Biophys. Acta 549, 1-29.Google Scholar
  21. Nicholls, D. G., and Locke, R. M. (1984). Physiol. Rev. 64, 1-64.Google Scholar
  22. Nobes, C. D., Brown, G. C., Olive, P. N., and Brand, M. D. (1990). J. Biol. Chem. 265, 12903-12909.Google Scholar
  23. Paulik, M. A., Buckholz, R. G., Lancaster, M. E., Dallas, W. S., Hull-Ryde, E. A., Weiel, J. E., and Lenhard, J. M. (1998). Pharmaceut. Res. 15, 944-949.Google Scholar
  24. Porter, R. K., and Brand, M. D. (1995a). Amer. J. Physiol. 268, R641-R650.Google Scholar
  25. Porter, R. K., and Brand, M. D. (1995b). Amer. J. Physiol. 269, R1213-1224.Google Scholar
  26. Porter, R. K., Hulbert, A. J., and Brand, M. D. (1996). Amer. J. Physiol. 271, R1550-1560.Google Scholar
  27. Prieto, S., Bouillaud, F., Ricquier, D., and Rial, E. (1992). Eur. J. Biochem. 208, 487-491.Google Scholar
  28. Prieto, S., Bouillaud, F., and Rial, E. (1995). Biochem. J. 307, 657-661.Google Scholar
  29. Ricquier, D. (1998). Intern. J. Obesity 22, S4.Google Scholar
  30. Rolfe, D. F. S., and Brand, M. D. (1996). Amer. J. Physiol. 271, C1380-1389.Google Scholar
  31. Rolfe, D. F. S., Newman, J. M. B., Buckingham, J. A., Clark, M. G., and Brand, M. D. (1999). Amer. J. Physiol., 276, C692-C699.Google Scholar
  32. Roucou, X., Manon, S., and Guérin, M. (1997). Biochim. Biophys Acta 1324, 120-132.Google Scholar
  33. Samec, S., Seydoux, J., and Dulloo, A. G. (1998). FASEB J. 12, 715-724.Google Scholar
  34. Sanchis, D., Busquets, S., Alvarez, B., Ricquier, D., Lopez-Soriano, F. J., and Argile, J. M. (1998). FEBS Lett. 436, 415-418.Google Scholar
  35. Sanchis, D., Fleury, C., Chomiki, N., Goubern, M., Huang, Q., Neverova, M., Grégoire, F., Easlick, J., Raimbault, S., Lévi-Meyrueis, C., Miroux, B., Collins, S., Seldin, M., Richard, D., Warden, C., Bouillaud, F., and Ricquier, D. (1998). J. Biol. Chem. 273, 34611-34615.Google Scholar
  36. Skulachev, V. P. (1998). Biochim. Biophys. Acta 1363, 100-124.Google Scholar

Copyright information

© Plenum Publishing Corporation 1999

Authors and Affiliations

  • Jeff A. Stuart
    • 1
    • 2
  • Kevin M. Brindle
    • 1
  • James A. Harper
    • 1
  • Martin D. Brand
    • 1
  1. 1.Department of BiochemistryUniversity of CambridgeCambridgeUK
  2. 2.MRC Dunn Human Nutrition UnitCambridgeUK

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