Faculty of Medicine, Institute of Biochemistry I, Goethe-University Frankfurt, Frankfurt, Germany.
Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Frankfurt, Germany.
Front Immunol. 2021 Feb 18;12:632526. doi: 10.3389/fimmu.2021.632526. eCollection 2021.
Studies over the past decade have revealed that metabolism profoundly influences immune responses. In particular, metabolism causes epigenetic regulation of gene expression, as a growing number of metabolic intermediates are substrates for histone post-translational modifications altering chromatin structure. One of these substrates is acetyl-coenzyme A (CoA), which donates an acetyl group for histone acetylation. Cytosolic acetyl-CoA is also a critical substrate for synthesis of fatty acids and sterols necessary for rapid cellular growth. One of the main enzymes catalyzing cytosolic acetyl-CoA formation is ATP-citrate lyase (ACLY). In addition to its classical function in the provision of acetyl-CoA for lipogenesis, ACLY contributes to epigenetic regulation through histone acetylation, which is increasingly appreciated. In this review we explore the current knowledge of ACLY and acetyl-CoA in mediating innate and adaptive immune responses. We focus on the role of ACLY in supporting lipogenesis in immune cells as well as on its impact on epigenetic alterations. Moreover, we summarize alternative sources of acetyl-CoA and their contribution to metabolic and epigenetic regulation in cells of the immune system.
过去十年的研究表明，新陈代谢深刻地影响着免疫反应。特别是，新陈代谢导致了基因表达的表观遗传调控，因为越来越多的代谢中间产物是组蛋白翻译后修饰的底物，这些修饰改变了染色质结构。其中一种底物是乙酰辅酶 A（CoA），它为组蛋白乙酰化提供乙酰基。细胞质中的乙酰 CoA 也是合成脂肪酸和胆固醇所必需的，这些物质对于快速的细胞生长至关重要。催化细胞质乙酰 CoA 形成的主要酶之一是三磷酸腺苷-柠檬酸裂解酶（ACLY）。除了其在提供乙酰 CoA 用于脂肪生成方面的经典功能外，ACLY 通过组蛋白乙酰化促进表观遗传调控，这一点越来越受到重视。在这篇综述中，我们探讨了 ACLY 和乙酰 CoA 在调节先天和适应性免疫反应中的最新知识。我们重点介绍了 ACLY 在支持免疫细胞中脂肪生成以及对表观遗传改变的影响中的作用。此外，我们总结了乙酰 CoA 的替代来源及其在免疫系统细胞中的代谢和表观遗传调控中的贡献。
