Abstract
The lack of energy conservation in brown adipose tissue mitochondria when prepared byconventional methods was established in the 1960s and was correlated with the thermogenicfunction of the tissue. In order to observe energy conservation, two requirements had to bemet: the removal of the endogenous fatty acids and the addition of a purine nucleotide. Thesetwo factors have been the essential tools that led to the discovery of the energy dissipationpathway, the uncoupling protein UCP1. The activity is regulated by these two ligands. Purinenucleotides bind from the cytosolic side of the protein and inhibit transport. Fatty acids actas seconds messengers of noradrenaline and increase the proton conductance. This reviewpresents a historical perspective of the steps that led to the discovery of UCP1, its regulation,and our current view on its mechanism of transport.
REFERENCES
Bouillaud, F., Casteilla, L., and Ricquier, D. (1992). Mol. Biol. Evol. 9, 970-975.
Bouillaud, F., Arechaga, I., Petit, P. X., Raimbault, S., Levi-Meyrueis, C., Casteilla, L., Laurent, M., Rial, E., and Ricquier, D. (1994). EMBO J. 13, 1990-1997.
Cunningham, S. A., Wiesinger, H., and Nicholls, D. G. (1986). Eur. J. Biochem. 157, 415-420.
Dierks, T., Stappen, R., and Krámer, R. (1994). In Molecular Biology of Mitochondrial Transport Systems(Forte, M., and Colombini, M., eds.), Springer-Verlag, Berlin, pp. 117-129.
Flatmark, T., and Pedersen, J. I. (1975). Biochim. Biophys. Acta 416, 53-103.
Foster, D. O., and Frydman, L. (1978). Can. J. Physiol. Pharmacol. 56, 110-122.
Garlid, K. D., Orosz, D. E., Modriansky, M., Vassanelli, M., and Jezek, P. (1996) J. Biol. Chem. 271, 2615-2620.
Garlid, K. D., Jaburek, M., and Jezek, P. (1998). FEBS Lett. 438, 10-14.
González-Barroso, M. M., Fleury, C., Arechaga, I., Zaragoza, P., Levi-Meyrueis, C., Raimbault, S., Bouillaud, F., and Rial, E. (1996). Eur. J. Biochem. 239, 445-450.
González-Barroso, M. M., Fleury, C., Levi-Meyrueis, C., Zaragoza, P., Bouillaud, F., and Rial, E. (1997). Biochemistry 36, 10930-10935.
González-Barroso, M. M., Fleury, C., Bouillaud, F., Nicholls, D. G., and Rial, E. (1998). J. Biol. Chem. 273, 15528-15532.
Hamilton, J. A., and Cistola, D. P. (1986). Proc. Natl. Acad. Sci. USA 83, 82-86.
Hittelman, K. J., Lindberg, O., and Cannon, B. (1969). Eur. J. Biochem. 11, 183-192.
Heaton, G. M., and Nicholls, D. G. (1976). Eur. J. Biochem. 67, 511-517.
Heaton, G. M., and Nicholls, D. G. (1977). Biochem. Soc. Trans. 5, 210-212.
Heaton, G. M., Wagenvoord, R. J., Kemp, A., and Nicholls, D. G. (1978). Eur. J. Biochem. 82, 515-521.
Krämer, R. (1998). Exp. Physiol. 83, 259-265.
Klingenberg, M., and Winkler, E. (1985). EMBO J. 4, 3087-3092.
Lin, C. S., and Klingenberg, M. (1982). Biochemistry 21, 2950-2956.
Locke, R. M., and Nicholls, D. G. (1981). FEBS Lett. 135, 249-252.
Locke, R. M., Rial, E., Scott, I. D., and Nicholls, D. G. (1982a). Eur. J. Biochem. 129, 373-380.
Locke, R. M., Rial, E., and Nicholls, D. G. (1982b). Eur. J. Biochem. 129, 381-387.
Nicholls, D. G. (1974a). Eur. J. Biochem. 49, 573-583.
Nicholls, D. G. (1974b). Eur. J. Biochem. 49, 585-593.
Nicholls, D. G. (1974c). Eur. J. Biochem. 50, 305-315.
Nicholls, D. G. (1976). Eur. J. Biochem. 62, 223-228.
Nicholls, D. G. (1977). Eur. J. Biochem. 77, 349-356.
Nicholls, D. G. (1979). Biochim. Biophys. Acta 549, 1-29.
Nicholls, D. G., and Heaton, G. M. (1978). In The Proton and Calcium Pumps(Azzone, A., Awron, M., Metcalfe, J. C., Quagliariello, E., and Siliprandi, N, eds.), Elsevier, Amsterdam, pp.309-318.
Nicholls, D. G., and Lindberg, O. (1972). FEBS Lett. 25, 61-64.
Nicholls, D. G., and Lindberg, O. (1973). Eur. J. Biochem. 37, 523-530.
Nicholls, D. G., and Locke, R. M. (1984). Physiol. Rev. 64, 1-64.
Nicholls, D. G., Grav, H. J., and Lindberg, O. (1972). Eur. J. Biochem. 31, 526-533.
Nicholls, D. G., Snelling, R., and Rial, E. (1984). Biochem. Soc. Trans. 12, 388-390.
Prusiner, S. B., Cannon, B., Ching, T. M., and Lindberg, O. (1968). Eur. J. Biochem. 7, 51-57.
Rafael, J., and Heldt, H. W. (1976). FEBS Lett. 63, 304-308.
Rafael, J., Ludolph, H.-J., and Hohorst, H.-J. (1969). Hoppe-Seyler's Z. Physiol. Chem. 350, 1121-1131.
Rafael, J., Fesser, W., and Nicholls, D. G. (1986). Amer. J. Physiol. 250, C228-C235.
Rial, E., and Nicholls, D. G. (1986). Eur. J. Biochem. 161, 689-694.
Rial, E., Poustie, A., and Nicholls, D. G. (1983). Eur. J. Biochem. 137, 197-203.
Rial, E., Arechaga, I., Sainz-de-la-Maza, E., and Nicholls, D. G. (1989). Eur. J. Biochem. 182, 187-193.
Rial, E., González-Barroso, M. M., Fleury, C., and Bouillaud, F. (1998). Biofactors 8, 209-219.
Ricquier, D., and Kader, J. C. (1976). Biochem. Biophys. Res. Commun. 73, 577-583.
Skulachev, V. P. (1991). FEBS Lett. 294, 158-162.
Smith, R. E., and Horwitz, B. A. (1969). Physiol. Rev. 49, 330-425.
Trayhurn, P., and Nicholls, D. G., eds. (1986). In Brown Adipose Tissue, Edward Arnold, London.
Viguera, A. R., Goñi, F. M., and Rial, E. (1992). Eur. J. Biochem. 210, 893-899.
Walker, J. E., and Runswick, M. J. (1993). J. Bioenerg. Biomembr. 25, 435-446.
Winkler, E., and Klingenberg, M. (1994). J. Biol. Chem. 269, 2508-2515.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Nicholls, D.G., Rial, E. A History of the First Uncoupling Protein, UCP1. J Bioenerg Biomembr 31, 399–406 (1999). https://doi.org/10.1023/A:1005436121005
Issue Date:
DOI: https://doi.org/10.1023/A:1005436121005