Bertholet Ambre M, Kirichok Yuriy
Department of Physiology, University of California San Francisco, San Francisco, CA, USA.
Handb Exp Pharmacol. 2019;251:143-159. doi: 10.1007/164_2018_138.
Uncoupling protein 1 (UCP1) is an integral protein of the inner mitochondrial membrane (IMM) that is expressed specifically in brown and beige fat depots. UCP1 is responsible for the production of heat to control core body temperature, the regulation of fat metabolism, and the energy balance. As an uncoupling protein, UCP1 transports H across the IMM in presence of long-chain fatty acids (FA), which makes brown fat mitochondria produce heat at the expense of ATP. However, the exact mechanism of UCP1 action has remained difficult to elucidate, because direct methods for studying currents generated by UCP1 were unavailable. Recently, the patch-clamp technique was successfully applied to brown and beige fat mitochondria to directly study H currents across the IMM and characterize UCP1 function. A new model of the UCP1 mechanism was proposed based on the patch-clamp analysis. In this model, both FA anions (FA) and H are transport substrates of UCP1, and UCP1 operates as a non-canonical FA/H symporter. Here, we summarize recent findings obtained with the patch-clamp technique that describe how UCP1 can transport not only H but also FA.
解偶联蛋白1（UCP1）是线粒体内膜（IMM）的一种整合蛋白，在棕色和米色脂肪组织中特异性表达。UCP1负责产热以控制核心体温、调节脂肪代谢和能量平衡。作为一种解偶联蛋白，UCP1在长链脂肪酸（FA）存在的情况下将质子（H⁺）转运穿过线粒体内膜，这使得棕色脂肪线粒体以消耗ATP为代价产生热量。然而，UCP1作用的确切机制一直难以阐明，因为缺乏研究UCP1产生电流的直接方法。最近，膜片钳技术成功应用于棕色和米色脂肪线粒体，以直接研究穿过线粒体内膜的质子电流并表征UCP1的功能。基于膜片钳分析提出了一种UCP1机制的新模型。在该模型中，脂肪酸阴离子（FA⁻）和质子（H⁺）都是UCP1的转运底物，并且UCP1作为一种非典型的FA⁻/H⁺同向转运体发挥作用。在此，我们总结了利用膜片钳技术获得的最新发现，这些发现描述了UCP1如何不仅能转运质子（H⁺），还能转运脂肪酸（FA）。
