Ricquier D, Bouillaud F
Centre de Recherche sur l'Endocrinologie Moléculaire et le Développement (CEREMOD), Centre National de la recherche Scientifique (CNRS-Unit 9078), 9 rue Jules Hetzel, 92190 Meudon, France.
Biochem J. 2000 Jan 15;345 Pt 2(Pt 2):161-79.
Animal and plant uncoupling protein (UCP) homologues form a subfamily of mitochondrial carriers that are evolutionarily related and possibly derived from a proton/anion transporter ancestor. The brown adipose tissue (BAT) UCP1 has a marked and strongly regulated uncoupling activity, essential to the maintenance of body temperature in small mammals. UCP homologues identified in plants are induced in a cold environment and may be involved in resistance to chilling. The biochemical activities and biological functions of the recently identified mammalian UCP2 and UCP3 are not well known. However, recent data support a role for these UCPs in State 4 respiration, respiration uncoupling and proton leaks in mitochondria. Moreover, genetic studies suggest 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 excessive supply of substrates in order to regulate the ATP level, the NAD(+)/NADH ratio and various metabolic pathways, and to contain superoxide production. A major goal will be the analysis of mice that either lack the UCP2 or UCP3 gene or overexpress these genes. Other aims will be to investigate the possible roles of UCP2 and UCP3 in response to oxidative stress, lipid peroxidation, inflammatory processes, fever and regulation of temperature in certain specific parts of the body.
动植物解偶联蛋白（UCP）同源物构成线粒体载体的一个亚家族，它们在进化上相关，可能起源于质子/阴离子转运体祖先。棕色脂肪组织（BAT）中的UCP1具有显著且受严格调控的解偶联活性，这对于小型哺乳动物维持体温至关重要。在植物中鉴定出的UCP同源物在寒冷环境中被诱导，可能参与抗寒过程。最近发现的哺乳动物UCP2和UCP3的生化活性和生物学功能尚不清楚。然而，最近的数据支持这些UCP在状态4呼吸、呼吸解偶联和线粒体质子泄漏中发挥作用。此外，遗传学研究表明UCP2和UCP3在人类能量消耗中起作用。UCPs还可能参与细胞代谢对底物过量供应的适应，以调节ATP水平、NAD(+)/NADH比率和各种代谢途径，并抑制超氧化物的产生。一个主要目标将是分析缺乏UCP2或UCP3基因或过表达这些基因的小鼠。其他目标将是研究UCP2和UCP3在应对氧化应激、脂质过氧化、炎症过程、发热以及身体某些特定部位的温度调节中的可能作用。
