The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP

Animal and plant uncoupling protein (UCP) homologues form a subfamily of mi tochondrial carriers that are evolutionarily related and possibly derived f rom a proton/anion transporter ancestor. The brown adipose tissue (BAT) UCP 1 has a marked and strongly regulated uncoupling activity, essential to the maintenance of body temperature in small mammals. UCP homologues identifie d in plants are induced in a cold environment and may be involved in resist ance to chilling. The biochemical activities and biological functions of th e recently identified mammalian UCP2 and UCP3 are not well known. However, recent data support a role for these UCPs in State 4 respiration, respirati on uncoupling and proton leaks in mitochondria. Moreover, genetic studies s uggest that UCP2 and UCP3 play a part in energy expenditure in humans. The UCPs may also be involved in adaptation of cellular metabolism to an excess ive supply of substrates in order to regulate the ATP level, the NAD(+)/NAD H ratio and various metabolic pathways, and to contain superoxide productio n. A major goal will be the analysis of mice that either lack the UCP2 or U CP3 gene or overexpress these genes. Other aims will be to investigate the possible roles of UCP2 and UCP3 in response to oxidative stress, lipid pero xidation, inflammatory processes, fever and regulation of temperature in ce rtain specific parts of the body.