Affourtit Charles, Crichton Paul G, Parker Nadeene, Brand Martin D
MRC Dunn Human Nutrition Unit, Hills Road, Cambridge CB2 2XY, UK.
Novartis Found Symp. 2007;287:70-80; discussion 80-91.
Mitochondria are incompletely coupled because of proton leaks that short-circuit oxidative phosphorylation. Basal proton leak is unregulated and is associated with the presence (but not catalytic activity) of the adenine nucleotide translocase. Inducible proton leak is regulated and is catalysed by the adenine nucleotide translocase and specific uncoupling proteins (UCPs). UCP1 catalyses proton conductance in mammalian brown adipose tissue. It is activated by fatty acids, which overcome nucleotide inhibition. UCP2, UCP3 and UCPs from birds, fish and plants also catalyse proton conductance that is inhibited by nucleotides. However, they require activation by superoxide or other reactive oxygen species (ROS). The mechanism of proton transport by the UCPs is unresolved. UCPs may also transport fatty acids or fatty acyl peroxides. Several physiological functions of UCPs are postulated. (1) UCP1 is specialised for thermogenesis; UCP3 and avian UCPs possibly share this function. (2) UCPs may attenuate ROS production and protect against oxidative damage, degenerative diseases and ageing. (3) UCP3 may catalyse fatty acid transport. (4) UCP2 has a signalling role in pancreatic beta cells, where it attenuates insulin secretion. Other roles remain to be discovered.
由于质子泄漏使氧化磷酸化短路，线粒体处于不完全偶联状态。基础质子泄漏不受调控，与腺嘌呤核苷酸转位酶的存在（而非催化活性）相关。可诱导的质子泄漏受调控，由腺嘌呤核苷酸转位酶和特定的解偶联蛋白（UCPs）催化。UCP1催化哺乳动物棕色脂肪组织中的质子传导。它被脂肪酸激活，脂肪酸可克服核苷酸抑制作用。来自鸟类、鱼类和植物的UCP2、UCP3及其他UCPs也催化受核苷酸抑制的质子传导。然而，它们需要超氧化物或其他活性氧（ROS）激活。UCPs质子转运的机制尚未明确。UCPs也可能转运脂肪酸或脂肪酰过氧化物。推测UCPs有多种生理功能。（1）UCP1专门用于产热；UCP3和鸟类UCPs可能具有此功能。（2）UCPs可能减少ROS生成，保护机体免受氧化损伤、退行性疾病和衰老影响。（3）UCP3可能催化脂肪酸转运。（4）UCP2在胰腺β细胞中具有信号传导作用，可减弱胰岛素分泌。其他作用还有待发现。
