Mitochondrial Uncoupler Proteins

Abstract

Mitochondrial uncoupling proteins (UCPs), members of a family of mitochondrial anion carrier proteins (MACP), are nuclear-encoded transmembrane transporter proteins located in the mitochondrial inner membrane. UCP1, mainly expressed in brown adipose tissue (BAT), was the first to be discovered and is responsible for animal thermogenesis; UCP2, originally thought to play a role in nonshivering thermogenesis, obesity and diabetes, its main function appears to be in the control of mitochondria-derived reactive oxygen species (ROS). Another uncoupling protein homologue, the UCP3 is mainly expressed in skeletal muscle and brown adipose tissue and its gene is transcribed from tissue-specific promoters in humans but not in rodents. All the members of this protein family possess a common feature of shunting protons across the mitochondrial inner membrane and reduce ATP synthesis; however, this common mechanism of action is used to carry out different functions by the different UCPs. The distribution and abundance of UCPs are tissue specific, which is also reflected into the processes that these proteins are thought to be participating. UCPs other than UCP1 are involved in several biological processes such as fatty acid (FA) metabolism, insulin secretion, oxidative stress (OS), heart pathophysiology and macrophage activation. New discoveries are advancing our understanding of UCPs roles in cardiovascular physiology.