Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.
Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.
Redox Biol. 2022 Dec;58:102553. doi: 10.1016/j.redox.2022.102553. Epub 2022 Nov 23.
Endogenous small molecules are metabolic regulators of cell function. Itaconate is a key molecule that accumulates in cells when the Krebs cycle is disrupted. Itaconate is derived from cis-aconitate decarboxylation by cis-aconitate decarboxylase (ACOD1) in the mitochondrial matrix and is also known as immune-responsive gene 1 (IRG1). Studies have demonstrated that itaconate plays an important role in regulating signal transduction and posttranslational modification through its immunoregulatory activities. Itaconate is also an important bridge among metabolism, inflammation, oxidative stress, and the immune response. This review summarizes the structural characteristics and classical pathways of itaconate, its derivatives, and the compounds that release itaconate. Here, the mechanisms of itaconate action, including its transcriptional regulation of ATF3/IκBζ axis and type I IFN, its protein modification regulation of KEAP1, inflammasome, JAK1/STAT6 pathway, TET2, and TFEB, and succinate dehydrogenase and glycolytic enzyme metabolic action, are presented. Moreover, the roles of itaconate in diseases related to inflammation and oxidative stress induced by autoimmune responses, viruses, sepsis and IRI are discussed in this review. We hope that the information provided in this review will help increase the understanding of cellular immune metabolism and improve the clinical treatment of diseases related to inflammation and oxidative stress.
内源性小分子是细胞功能的代谢调节剂。衣康酸是一种关键分子，当三羧酸循环被破坏时，它会在细胞中积累。衣康酸来源于顺式乌头酸的脱羧，由线粒体基质中的顺式乌头酸脱羧酶 1（ACOD1）催化，也被称为免疫反应基因 1（IRG1）。研究表明，衣康酸通过其免疫调节活性在调节信号转导和翻译后修饰中发挥重要作用。衣康酸还是代谢、炎症、氧化应激和免疫反应之间的重要桥梁。本文综述了衣康酸及其衍生物和释放衣康酸的化合物的结构特征和经典途径。本文介绍了衣康酸的作用机制，包括其对 ATF3/IκBζ 轴和 I 型 IFN 的转录调控、对 KEAP1、炎症小体、JAK1/STAT6 通路、TET2 和 TFEB 的蛋白修饰调控，以及对琥珀酸脱氢酶和糖酵解酶代谢的作用。此外，本文还讨论了衣康酸在自身免疫反应、病毒、脓毒症和 IRI 引起的与炎症和氧化应激相关的疾病中的作用。我们希望本文提供的信息将有助于增加对细胞免疫代谢的理解，并改善与炎症和氧化应激相关疾病的临床治疗。
