(5) UNCOUPLING PROTEINS

F. Bouillaud (1), C. Fleury (1), MdM Gonzalez Barroso (2), C. Pecqueur (1), M. Goubern (3), D. Ricquier (1) and E. Rial (2)
(1) ceremod C.N.R.S. 9 rue J. Hetzel 92190 Meudon FRANCE
(2) C.I.B. C.S.I.C. 144 c/ Velazquez 28006 Madrid SPAIN
(3) E.P.H.E. I.N.R.A. 78352 Jouy en Josas FRANCE

Several new genes coding for protein homologous to the brown adipose tissue uncoupling protein have been described recently. Accordingly brown adipose tissue UCP is called UCP1 and the new genes are called UCP2 [1] and UCP3 [2,3], UCP3 is expressed specifically in skeletal muscle whereas UCP2 is found in many tissues. An homolog has been found also in plants [4]. These new members of the family of mitochondrial anion carriers are expected to participate to the proton leak found in mitochondria under state 4.

The overexpression in yeast is used to assay for the uncoupling activity of such proteins. Overexpression of UCP2 is accompanied by modifications of the growth rate and of the mitochondrial staining with the potential sensitive probe DiOC(6)3 that are similar to the effects obtained with UCP1. In isolated yeast mitochondria presence of the UCP2 results in a higher state 4. Known regulators of the UCP1 (nucleotides and fatty acids) have no significant effects on the UCP2. Therefore the regulators of UCP2 or of UCP3 are yet to be defined.

[1] Fleury C et al. (1997) Nature Genetics 15:269-272.
[2] Boss O et al. (1997) FEBS Lett. 408:39-42.
[3] Vidal-Puig A, Solanes G, Grujic D, Flier JS, Lowell BB (1997) Biochem. Biophys. Res. Commun. 235:79-82.
[4] Laloi M. et al. (1997) Nature 389:135-136.