The role of uncoupling proteins in pathophysiological states

Until very recently, the uncoupling protein-1 (UCP1), present only in brown adipose tissue (BAT), was considered to be the only mitochondrial carrier protein that stimulated heat production by dissipating the proton gradient generated during respiration across the inner mitochondrial membrane and therefore uncoupling respiration from ATP synthesis. Recently, new uncoupling proteins, UCP2, UCP3, and UCP4, and brain mitochondrial carrier protein-1 (BMCP-1) have been described in mammalian tissues. The present review deals with the possible role of these proteins in different pathological conditions involving alterations in energy balance such as obesity or cachexia. In conclusion, the emergence of the UCP family has altered the approaches to bioenergetics and stressed the importance of uncoupling respiration in different pathophysiological conditions. An extensive qualitative and quantitative characterization of the new members of the UCP family in mammalian tissues will allow a better understanding of the molecular and regulatory mechanisms of thermogenesis and energy metabolism. At this point, we hope that the knowledge presented in the present review will not only stimulate a debate about the role of the UCP family in disease but also lead to applications beneficial for human health.