Exploring the Role of ATP-Citrate Lyase in the Immune System.
Exploring the Role of ATP-Citrate Lyase in the Immune System.
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DOI：
10.3389/fimmu.2021.632526
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发表时间：
2021
影响因子：
7.3
通讯作者：
Namgaladze D
中科院分区：
文献类型：
--
作者：
Dominguez M;Brüne B;Namgaladze D
过去十年的研究表明，新陈代谢深刻影响免疫反应。特别是，代谢导致基因表达的表观遗传调控，因为越来越多的代谢中间体是组蛋白翻译后修饰改变染色质结构的底物。这些底物之一是乙酰辅酶A（CoA），其为组蛋白乙酰化提供乙酰基。胞质乙酰辅酶A也是细胞快速生长所必需的脂肪酸和甾醇从头合成的关键底物。催化细胞溶质乙酰辅酶A形成的主要酶之一是ATP-柠檬酸裂解酶（ACLY）。除了其提供乙酰辅酶A用于从头脂肪生成的经典功能外，ACLY还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，我们探讨了目前的知识ACLY和乙酰辅酶A介导的先天性和适应性免疫反应。我们专注于ACLY在支持免疫细胞从头脂肪生成中的作用以及其对表观遗传改变的影响。此外，我们总结了乙酰辅酶A的替代来源及其对免疫系统细胞代谢和表观遗传调节的贡献。
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 de novo 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 de novo 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 de novo 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.
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影响因子：
8
作者：
Bauer, DE;Hatzivassiliou, G;Thompson, CB
通讯作者：
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影响因子：
4.8
作者：
Beigneux, AP;Kosinski, C;Young, SG
通讯作者：
Young, SG
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影响因子：
4.8
作者：
Berwick, DC;Hers, I;Tavaré, JM
通讯作者：
Tavaré, JM
影响因子：
4.8
作者：
Dufort, Fay J.;Gumina, Maria R.;Chiles, Thomas C.
通讯作者：
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