Mitochondrial proton leaks and uncoupling proteins

Non-shivering thermogenesis in brown adipose tissue is mediated by uncoupling protein 1 (UCP1), which provides a carefully regulated proton re-entry pathway across the mitochondrial inner membrane operating in parallel to the ATP synthase and allowing respiration, and hence thermogenesis, to be released from the constraints of respiratory control. In the 40 years since UCP1 was first described, an extensive, and frequently contradictory, literature has accumulated, focused on the acute physiological regulation of the protein by fatty acids, purine nucleotides and possible additional factors. The purpose of this review is to examine, in detail, the experimental evidence underlying these proposed mechanisms. Emphasis will be placed on the methodologies employed and their relation to the physiological constraints under which the protein functions in the intact cell. The nature of the endogenous, UCP1-independent, proton leak will also be discussed. Finally, the troubled history of the putative novel uncoupling proteins, UCP2 and UCP3, will be evaluated.

Automated summary

This review examines the mechanisms underlying non-shivering thermogenesis in brown adipose tissue mediated by UCP1, emphasizing the experimental evidence and physiological constraints. It also discusses the nature of endogenous proton leak and evaluates the troubled history of putative novel uncoupling proteins UCP2 and UCP3.