Porter R K
Department of Biochemistry, Trinity College Dublin, Dublin 2, Ireland.
Biochim Biophys Acta. 2001 Mar 1;1504(1):120-7. doi: 10.1016/s0005-2728(00)00246-2.
In mitochondria ATP synthesis is not perfectly coupled to oxygen consumption due to proton leak across the mitochondrial inner membrane. Quantitative studies have shown that proton leak contributes to approximately 25% of the resting oxygen consumption of mammals. Proton leak plays a role in accounting for differences in basal metabolic rate. Thyroid studies, body mass studies, phylogenic studies and obesity studies have all shown that increased mass-specific metabolic rate is linked to increased mitochondrial proton leak. The mechanism of the proton leak is unclear. Evidence suggests that proton leak occurs by a non-specific diffusion process across the mitochondrial inner membrane. However, the high degree of sequence homology of the recently cloned uncoupling proteins UCP 2 and UCP 3 to brown adipose tissue UCP 1, and their extensive tissue distribution, suggest that these novel uncoupling proteins play a role in proton leak. Early indications from reconstitution experiments and several in vitro expression studies suggest that the novel uncoupling proteins uncouple mitochondria. Furthermore, mice overexpressing UCP 3 certainly show a phenotype consistent with increased metabolism. The evidence for a role for these novel UCPs in mitochondrial proton leak is reviewed.
在线粒体中，由于质子跨线粒体内膜泄漏，ATP合成与氧消耗并非完美偶联。定量研究表明，质子泄漏约占哺乳动物静息氧消耗的25%。质子泄漏在解释基础代谢率差异方面发挥作用。甲状腺研究、体重研究、系统发育研究和肥胖研究均表明，质量特异性代谢率增加与线粒体质子泄漏增加有关。质子泄漏的机制尚不清楚。有证据表明，质子泄漏是通过跨线粒体内膜的非特异性扩散过程发生的。然而，最近克隆的解偶联蛋白UCP 2和UCP 3与棕色脂肪组织UCP 1的高度序列同源性及其广泛的组织分布表明，这些新型解偶联蛋白在质子泄漏中发挥作用。重组实验和一些体外表达研究的早期迹象表明，新型解偶联蛋白使线粒体解偶联。此外，过度表达UCP 3的小鼠确实表现出与代谢增加一致的表型。本文综述了这些新型UCPs在线粒体质子泄漏中作用的证据。
