Liu Hongling, Negoita Florentina, Brook Matthew, Sakamoto Kei, Morton Nicholas M
Molecular Metabolism Group, University/BHF Centre for Cardiovascular Sciences, Queens Medical Research Institute, University of Edinburgh, U.K.
Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen 2200, Denmark.
Essays Biochem. 2024 Dec 4;68(4):467-478. doi: 10.1042/EBC20230095.
Hydrogen sulfide (H2S) played a pivotal role in the early evolution of life on Earth before the predominance of atmospheric oxygen. The legacy of a persistent role for H2S in life's processes recently emerged through its discovery in modern biochemistry as an endogenous cellular signalling modulator involved in numerous biological processes. One major mechanism through which H2S signals is protein cysteine persulfidation, an oxidative post-translational modification. In recent years, chemoproteomic technologies have been developed to allow the global scanning of protein persulfidation targets in mammalian cells and tissues, providing a powerful tool to elucidate the broader impact of altered H2S in organismal physiological health and human disease states. While hundreds of proteins were confirmed to be persulfidated by global persulfidome methodologies, the targeting of specific proteins of interest and the investigation of further mechanistic studies are still underdeveloped due to a lack of stringent specificity of the methods and the inherent instability of persulfides. This review provides an overview of the processes of endogenous H2S production, oxidation, and signalling and highlights the application and limitations of current persulfidation labelling approaches for investigation of this important evolutionarily conserved biological switch for protein function.
在大气氧占主导地位之前，硫化氢（H₂S）在地球生命的早期演化中发挥了关键作用。近年来，随着H₂S在现代生物化学中作为一种参与众多生物过程的内源性细胞信号调节剂被发现，其在生命过程中持续发挥作用的遗留影响也逐渐显现。H₂S信号传导的一个主要机制是蛋白质半胱氨酸过硫化，这是一种氧化后修饰。近年来，化学蛋白质组学技术得到了发展，可用于在哺乳动物细胞和组织中对蛋白质过硫化靶点进行全局扫描，为阐明H₂S变化对机体生理健康和人类疾病状态的更广泛影响提供了有力工具。虽然通过全局过硫化蛋白质组学方法已确认数百种蛋白质会发生过硫化，但由于方法缺乏严格的特异性以及过硫化物固有的不稳定性，针对特定感兴趣蛋白质的靶向研究以及进一步的机制研究仍不够完善。本综述概述了内源性H₂S产生、氧化和信号传导的过程，并强调了当前用于研究这种重要的、在进化上保守的蛋白质功能生物开关的过硫化标记方法的应用及局限性。
