Mitochondrial proton leak and the uncoupling protein 1 homologues.

Mitochondrial proton leak is the largest single contributor to the standard metabolic rate (SMR) of a rat, accounting for about 20% of SMR. Yet the mechanisms by which proton leak occurs are incompletely understood. The available evidence suggests that both phospholipids and proteins in the mitochondrial inner membrane are important determinants of proton conductance. The uncoupling protein 1 homologues (e.g. UCP2, UCP3) may play a role in mediating proton leak, but it is unlikely they account for all of the observed proton conductance. Experimental data regarding the functions of these proteins include important ambiguities and contradictions which must be addressed before their function can be confirmed. The physiological role of the proton leak, and of the uncoupling protein 1 homologues, remains similarly unclear.