Bak D W, Weerapana E
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467, USA.
Mol Biosyst. 2015 Mar;11(3):678-97. doi: 10.1039/c4mb00571f. Epub 2014 Dec 18.
The mitochondria are critical mediators of cellular redox homeostasis due to their role in the generation and dissipation of reactive oxygen/nitrogen species (ROS/RNS). Modulations in ROS/RNS levels in the mitochondria are often reflected through oxidation/nitrosation of highly redox-sensitive cysteine residues within this organelle. Oxidation/nitrosation of functional cysteines on mitochondrial proteins serves to modulate protein activity, localization, and complexation in response to cellular stress, thereby controlling critical processes such as oxidative phosphorylation, apoptosis, and redox signalling. In this review, we describe mitochondrial sources of ROS/RNS, cysteine modifications that are triggered by increased mitochondrial ROS/RNS, and examples of key mitochondrial proteins that are regulated through cysteine-mediated redox signalling. We highlight recent advancements in proteomic methods to study cysteine posttranslational modifications. These tools will further aid in illuminating the important role of cysteine in maintaining and transducing redox signals in the mitochondria.
线粒体是细胞氧化还原稳态的关键调节因子，因为它们在活性氧/氮物种（ROS/RNS）的产生和消散中发挥作用。线粒体中ROS/RNS水平的调节通常通过该细胞器内高度氧化还原敏感的半胱氨酸残基的氧化/亚硝化反应来体现。线粒体蛋白质上功能性半胱氨酸的氧化/亚硝化反应可调节蛋白质活性、定位和复合物形成，以应对细胞应激，从而控制诸如氧化磷酸化、细胞凋亡和氧化还原信号传导等关键过程。在本综述中，我们描述了ROS/RNS的线粒体来源、线粒体ROS/RNS增加引发的半胱氨酸修饰，以及通过半胱氨酸介导的氧化还原信号传导调节的关键线粒体蛋白实例。我们强调了蛋白质组学方法在研究半胱氨酸翻译后修饰方面的最新进展。这些工具将进一步有助于阐明半胱氨酸在维持和转导线粒体氧化还原信号中的重要作用。
