Buck Institute for Research on Aging, Novato, CA, USA.
Biochim Biophys Acta Bioenerg. 2021 Jul 1;1862(7):148428. doi: 10.1016/j.bbabio.2021.148428. Epub 2021 Mar 31.
Non-shivering thermogenesis in brown adipose tissue is mediated by uncoupling protein 1 (UCP1), which provides a carefully regulated proton re-entry pathway across the mitochondrial inner membrane operating in parallel to the ATP synthase and allowing respiration, and hence thermogenesis, to be released from the constraints of respiratory control. In the 40 years since UCP1 was first described, an extensive, and frequently contradictory, literature has accumulated, focused on the acute physiological regulation of the protein by fatty acids, purine nucleotides and possible additional factors. The purpose of this review is to examine, in detail, the experimental evidence underlying these proposed mechanisms. Emphasis will be placed on the methodologies employed and their relation to the physiological constraints under which the protein functions in the intact cell. The nature of the endogenous, UCP1-independent, proton leak will also be discussed. Finally, the troubled history of the putative novel uncoupling proteins, UCP2 and UCP3, will be evaluated.
棕色脂肪组织中的非颤抖性产热是由解偶联蛋白 1（UCP1）介导的，它提供了一条经过线粒体内膜的质子再进入途径，与 ATP 合酶平行运作，使呼吸作用以及产热作用能够摆脱呼吸控制的限制。自 UCP1 首次被描述以来的 40 年中，积累了大量的文献，这些文献主要集中在蛋白质的急性生理调节上，涉及脂肪酸、嘌呤核苷酸以及可能的其他因素。本综述的目的是详细检查这些拟议机制的实验证据。重点将放在所使用的方法及其与蛋白质在完整细胞中发挥作用时的生理限制的关系上。内源性、UCP1 非依赖性质子泄漏的性质也将被讨论。最后，将对假定的新型解偶联蛋白 UCP2 和 UCP3 的混乱历史进行评估。
