Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, Kentucky, USA.
J.G. Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA.
J Leukoc Biol. 2019 Aug;106(2):359-367. doi: 10.1002/JLB.3RU1218-496R. Epub 2019 Feb 15.
The tricarboxylic acid (TCA) cycle is a mitochondrial metabolic hub that coordinates the metabolism of carbohydrates, proteins, and fats into carbon dioxide and ATP. At specific points in the cycle, the diversion, import, or export of TCA metabolites allows for the dynamic regulation of a variety of tissue and/or cell-specific phenotypic processes. Recent studies have identified that a number of TCA metabolites are important in controlling monocyte/macrophage phenotypes and effector functions while specific macrophage activation or polarization states functionally determine the relative utilization of each. This review focuses on the metabolic reprogramming of the TCA cycle in macrophages and how individual metabolites play a variety of context-specific roles in determining physiologic and pathologic macrophage activation and homeostatic functions. We discuss the implications of these findings and address unanswered questions regarding the role of the TCA cycle in guiding macrophage-dependent immune responses.
三羧酸（TCA）循环是线粒体代谢枢纽，协调碳水化合物、蛋白质和脂肪代谢为二氧化碳和 ATP。在循环的特定点，TCA 代谢物的分流、导入或导出允许对各种组织和/或细胞特异性表型过程进行动态调节。最近的研究表明，许多 TCA 代谢物在控制单核细胞/巨噬细胞表型和效应功能方面很重要，而特定的巨噬细胞激活或极化状态则在功能上决定了每种代谢物的相对利用。本综述重点介绍了 TCA 循环在巨噬细胞中的代谢重编程，以及单个代谢物如何在决定生理和病理巨噬细胞激活和稳态功能方面发挥各种特定于情境的作用。我们讨论了这些发现的意义，并探讨了关于 TCA 循环在指导巨噬细胞依赖性免疫反应中的作用的未解决问题。
