Department of Biochemistry, Microbiology, and Immunology, University of Ottawa Faculty of Medicine, Ottawa, ON, Canada K1G8M5.
Free Radic Biol Med. 2011 Sep 15;51(6):1106-15. doi: 10.1016/j.freeradbiomed.2011.06.022. Epub 2011 Jun 24.
Reactive oxygen species (ROS), natural by-products of aerobic respiration, are important cell signaling molecules, which left unchecked can severely impair cellular functions and induce cell death. Hence, cells have developed a series of systems to keep ROS in the nontoxic range. Uncoupling proteins (UCPs) 1-3 are mitochondrial anion carrier proteins that are purported to play important roles in minimizing ROS emission from the electron transport chain. The function of UCP1 in this regard is highly contentious. However, UCPs 2 and 3 are generally thought to be activated by ROS or ROS by-products to induce proton leak, thus providing a negative feedback loop for mitochondrial ROS production. In our laboratory, we have not only confirmed that ROS activate UCP2 and UCP3, but also demonstrated that UCP2 and UCP3 are controlled by covalent modification by glutathione. Furthermore, the reversible glutathionylation is required to activate/inhibit UCP2 and UCP3, but not UCP1. Hence, our findings are consistent with the notion that UCPs 2 and 3 are acutely activated by ROS, which then directly modulate the glutathionylation status of the UCP to decrease ROS emission and participate in cell signaling mechanisms.
活性氧（ROS）是需氧呼吸的天然副产物，是重要的细胞信号分子。如果ROS 不受控制，会严重损害细胞功能并诱导细胞死亡。因此，细胞已经开发出一系列系统来将 ROS 保持在无毒范围内。解偶联蛋白（UCP）1-3 是线粒体阴离子载体蛋白，据推测它们在最小化电子传递链中 ROS 的释放方面发挥着重要作用。UCP1 在这方面的功能存在很大争议。然而，UCP2 和 UCP3 通常被认为是被 ROS 或 ROS 副产物激活以诱导质子泄漏，从而为线粒体 ROS 产生提供负反馈回路。在我们的实验室中，我们不仅证实了 ROS 可以激活 UCP2 和 UCP3，还证明了 UCP2 和 UCP3 受到谷胱甘肽的共价修饰控制。此外，需要可逆的谷胱甘肽化来激活/抑制 UCP2 和 UCP3，但不能激活 UCP1。因此，我们的发现与 ROS 可以直接激活 UCP2 和 UCP3 的观点一致，然后直接调节 UCP 的谷胱甘肽化状态，以减少 ROS 的释放并参与细胞信号机制。
