Use the Protonmotive Force: Mitochondrial Uncoupling and Reactive Oxygen Species.
Use the Protonmotive Force: Mitochondrial Uncoupling and Reactive Oxygen Species.
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DOI：
10.1016/j.jmb.2018.03.025
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发表时间：
2018-10-19
影响因子：
5.6
通讯作者：
Wojtovich AP
中科院分区：
文献类型：
--
作者：
Berry BJ;Trewin AJ;Amitrano AM;Kim M;Wojtovich AP
线粒体呼吸导致跨线粒体内膜(IM)的电化学质子梯度或质子动势(PMF)。PMF是一种由电荷(Δψm)和化学成分(ΔpH)组成的势能，它们共同驱动三磷酸腺苷的产生。在一个称为解偶联的过程中，质子泄漏到线粒体基质中，而不依赖于ATP的产生，分散了PMF，能量以热量的形式损失。其他事件也可以直接消散PMF，而不依赖于ATP的产生，例如化学暴露或涉及调控的线粒体膜电解质转运的机制。解偶联在代谢可塑性中具有明确的作用，并可通过信号转导与生理事件联系起来。在后一种情况下，PMF影响线粒体活性氧(ROS)的产生。虽然ROS具有分子损伤的能力，但它也具有依赖于其产生的时间、位置和数量的信号特性。在这篇综述中，我们概述了线粒体ROS的产生，解偶联的机制，以及这些机制是如何协同作用影响生理和病理的，包括：肥胖、心血管疾病和免疫。总体而言，我们强调，孤立的生物能量模型-线粒体和细胞-仅部分概括了体内PMF和ROS信号之间的复杂联系。
Mitochondrial respiration results in an electrochemical proton gradient, or protonmotive force (pmf), across the mitochondrial inner membrane (IM). The pmf is a form of potential energy consisting of charge (Δψm) and chemical (ΔpH) components, that together drive ATP production. In a process called uncoupling, proton leak into the mitochondrial matrix independent of ATP production dissipates the pmf and energy is lost as heat. Other events can directly dissipate the pmf independent of ATP production as well, such as chemical exposure or mechanisms involving regulated mitochondrial membrane electrolyte transport. Uncoupling has defined roles in metabolic plasticity and can be linked through signal transduction to physiologic events. In the latter case, the pmf impacts mitochondrial reactive oxygen species (ROS) production. Though capable of molecular damage, ROS also have signaling properties that depend on the timing, location, and quantity of their production. In this review we provide a general overview of mitochondrial ROS production, mechanisms of uncoupling, and how these work in tandem to affect physiology and pathologies, including: obesity, cardiovascular disease, and immunity. Overall, we highlight that isolated bioenergetic models—mitochondria and cells—only partially recapitulate the complex link between the pmf and ROS signaling that occurs in vivo.
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