Institute of Structural and Molecular Biology, University College London, Gower Street, London WC1E 6BT, U.K.
Biochem Soc Trans. 2018 Jun 19;46(3):721-728. doi: 10.1042/BST20170506. Epub 2018 May 25.
In a diverse family of cellular cofactors, coenzyme A (CoA) has a unique design to function in various biochemical processes. The presence of a highly reactive thiol group and a nucleotide moiety offers a diversity of chemical reactions and regulatory interactions. CoA employs them to activate carbonyl-containing molecules and to produce various thioester derivatives (e.g. acetyl CoA, malonyl CoA and 3-hydroxy-3-methylglutaryl CoA), which have well-established roles in cellular metabolism, production of neurotransmitters and the regulation of gene expression. A novel unconventional function of CoA in redox regulation, involving covalent attachment of this coenzyme to cellular proteins in response to oxidative and metabolic stress, has been recently discovered and termed protein CoAlation (S-thiolation by CoA or CoAthiolation). A diverse range of proteins was found to be CoAlated in mammalian cells and tissues under various experimental conditions. Protein CoAlation alters the molecular mass, charge and activity of modified proteins, and prevents them from irreversible sulfhydryl overoxidation. This review highlights the role of a key metabolic integrator CoA in redox regulation in mammalian cells and provides a perspective of the current status and future directions of the emerging field of protein CoAlation.
在细胞辅助因子的多样化家族中，辅酶 A（CoA）具有独特的设计，可在各种生化过程中发挥作用。高反应性巯基和核苷酸部分的存在提供了多种化学反应和调节相互作用。CoA 利用它们来激活含有羰基的分子，并产生各种硫酯衍生物（例如乙酰 CoA、丙二酰 CoA 和 3-羟基-3-甲基戊二酰 CoA），这些衍生物在细胞代谢、神经递质的产生和基因表达的调节中具有明确的作用。最近发现了辅酶 A 在氧化还原调节中的一种新的非常规功能，涉及在氧化和代谢应激下，将这种辅酶共价连接到细胞蛋白上，这一功能被称为蛋白质 CoAlation（CoA 对蛋白质的巯基化或 CoA 硫醇化）。在各种实验条件下，在哺乳动物细胞和组织中发现了多种蛋白质发生 CoAlation。蛋白质 CoAlation 改变了修饰蛋白的分子量、电荷和活性，并防止它们发生不可逆的巯基过度氧化。这篇综述强调了关键代谢调节剂 CoA 在哺乳动物细胞氧化还原调节中的作用，并提供了当前蛋白质 CoAlation 领域的现状和未来发展方向的视角。
