Abstract

Overproduction of reactive oxygen species and compromised antioxidant defenses perturb intracellular redox homeostasis and is associated with a myriad of human diseases as well as with the natural process of aging. Hydrogen sulfide (H₂S), which is biosynthesized by organisms ranging from bacteria to man, influences a broad range of physiological functions. A highly touted molecular mechanism by which H₂S exerts its cellular effects is via post-translational modification of the thiol redox proteome, converting cysteine thiols to persulfides, in a process referred to as protein persulfidation. The physiological relevance of this modification in the context of specific signal transmission pathways remains to be rigorously established, while a general protective role for protein persulfidation against hyper-oxidation of the cysteine proteome is better supported. A second mechanism by which H₂S modulates redox homeostasis is via remodeling the redox metabolome, targeting the electron transfer chain and perturbing the major redox nodes i.e. CoQ/CoQH₂, NAD⁺/NADH and FAD/FADH₂. The metabolic changes that result from H₂S-induced redox changes fan out from the mitochondrion to other compartments. In this review, we discuss recent developments in elucidating the roles of H₂S and its oxidation products on redox homeostasis and its role in protecting the thiol proteome.

摘要

活性氧的过量产生和抗氧化防御受损会扰乱细胞内氧化还原稳态，并与无数人类疾病以及自然衰老过程有关。硫化氢 (H ₂ S) 是由从细菌到人类的生物合成的，它影响广泛的生理功能。一种高度吹捧的分子机制，其中 H ₂S 发挥其细胞作用是通过硫醇氧化还原蛋白质组的翻译后修饰，将半胱氨酸硫醇转化为过硫化物，这一过程称为蛋白质过硫化。这种修饰在特定信号传输途径背景下的生理相关性仍有待严格确定，而蛋白质过硫化对半胱氨酸蛋白质组过氧化的一般保护作用得到了更好的支持。_{H 2} S 调节氧化还原稳态的第二种机制是通过重塑氧化还原代谢组，靶向电子转移链并扰乱主要的氧化还原节点，即 CoQ/CoQH ₂、NAD ⁺ /NADH 和 FAD/FADH ₂。_{H 2}引起的代谢变化S 诱导的氧化还原变化从线粒体散布到其他隔室。在这篇综述中，我们讨论了阐明 H ₂ S 及其氧化产物对氧化还原稳态的作用及其在保护硫醇蛋白质组中的作用的最新进展。