School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Front Immunol. 2018 Feb 5;9:141. doi: 10.3389/fimmu.2018.00141. eCollection 2018.
Metabolism in immune cells is no longer thought of as merely a process for adenosine triphosphate (ATP) production, biosynthesis, and catabolism. The reprogramming of metabolic pathways upon activation is also for the production of metabolites that can act as immune signaling molecules. Activated dendritic cells (DCs) and macrophages have an altered Krebs cycle, one consequence of which is the accumulation of both citrate and succinate. Citrate is exported from the mitochondria the mitochondrial citrate- carrier. Cytosolic metabolism of citrate to acetyl-coenzyme A (acetyl-CoA) is important for both fatty-acid synthesis and protein acetylation, both of which have been linked to macrophage and DC activation. Citrate-derived itaconate has a direct antibacterial effect and also has been shown to act as an anti-inflammatory agent, inhibiting succinate dehydrogenase. These findings identify citrate as an important metabolite for macrophage and DC effector function.
免疫细胞中的代谢不再仅仅被认为是产生三磷酸腺苷（ATP）、生物合成和分解代谢的过程。代谢途径的重新编程也是为了产生可以作为免疫信号分子的代谢物。激活的树突状细胞（DC）和巨噬细胞有一个改变的克雷布斯循环，其结果之一是柠檬酸和琥珀酸的积累。柠檬酸从线粒体经线粒体柠檬酸载体被输出。细胞质中柠檬酸转化为乙酰辅酶 A（乙酰 CoA）对于脂肪酸合成和蛋白质乙酰化都很重要，这两者都与巨噬细胞和 DC 的激活有关。柠檬酸衍生的衣康酸具有直接的抗菌作用，并且已被证明是一种抗炎剂，抑制琥珀酸脱氢酶。这些发现确定了柠檬酸作为巨噬细胞和 DC 效应功能的重要代谢物。
