Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL, Canada.
Adv Exp Med Biol. 2019;1158:197-216. doi: 10.1007/978-981-13-8367-0_11.
Mitochondria are dynamic organelles that perform a number of interconnected tasks that are elegantly intertwined with the regulation of cell functions. This includes the provision of ATP, reactive oxygen species (ROS), and building blocks for the biosynthesis of macromolecules while also serving as signaling platforms for the cell. Although the functions executed by mitochondria are complex, at its core these roles are, to a certain degree, fulfilled by electron transfer reactions and the establishment of a protonmotive force (PMF). Indeed, mitochondria are energy conserving organelles that extract electrons from nutrients to establish a PMF, which is then used to drive ATP and NADPH production, solute import, and many other functions including the propagation of cell signals. These same electrons extracted from nutrients are also used to produce ROS, pro-oxidants that can have potentially damaging effects at high levels, but also serve as secondary messengers at low amounts. Mitochondria are also enriched with antioxidant defenses, which are required to buffer cellular ROS. These same redox buffering networks also fulfill another important role; regulation of proteins through the reversible oxidation of cysteine switches. The modification of cysteine switches with the antioxidant glutathione, a process called protein S-glutathionylation, has been found to play an integral role in controlling various mitochondrial functions. In addition, recent findings have demonstrated that disrupting mitochondrial protein S-glutathionylation reactions can have some dire pathological consequences. Accordingly, this chapter focuses on the role of mitochondrial cysteine switches in the modulation of different physiological functions and how defects in these pathways contribute to the development of disease.
线粒体是具有动态的细胞器，执行着许多相互关联的任务，这些任务与细胞功能的调节优雅地交织在一起。这包括提供 ATP、活性氧（ROS）和生物合成大分子的构建块，同时作为细胞的信号平台。虽然线粒体执行的功能很复杂，但从核心上讲，这些功能在一定程度上是通过电子转移反应和质子动力势（PMF）的建立来实现的。事实上，线粒体是能量守恒的细胞器，它从营养物质中提取电子来建立 PMF，然后利用 PMF 来驱动 ATP 和 NADPH 的产生、溶质的输入以及许多其他功能，包括细胞信号的传播。从营养物质中提取的这些电子也被用来产生 ROS，即具有潜在破坏性的氧化剂，但在低浓度下也可以作为次级信使。线粒体还富含抗氧化防御系统，这些防御系统是缓冲细胞内 ROS 所必需的。这些相同的氧化还原缓冲网络还具有另一个重要作用；通过半胱氨酸开关的可逆氧化来调节蛋白质。抗氧化谷胱甘肽对半胱氨酸开关的修饰，即蛋白质 S-谷胱甘肽化过程，已被发现在控制各种线粒体功能中起着重要作用。此外，最近的研究发现，破坏线粒体蛋白质 S-谷胱甘肽化反应可能会产生一些严重的病理后果。因此，本章重点介绍线粒体半胱氨酸开关在调节不同生理功能中的作用，以及这些途径的缺陷如何导致疾病的发展。
