生物
免疫系统
乌头酸酶
延胡索酶
柠檬酸循环
富马酸还原酶
富马酸二甲酯
下调和上调
生物化学
线粒体
琥珀酸脱氢酶
免疫学
酶
基因
多发性硬化
作者
Christian G. Peace,Shane M. O’Carroll,Luke O'neill
标识
DOI:10.1016/j.tcb.2023.10.005
摘要
Tricarboxylic acid (TCA) cycle metabolites have been implicated in modulating signalling pathways in immune cells. Notable examples include succinate and itaconate, which have pro- and anti-inflammatory roles, respectively. Recently, fumarate has emerged as having specific roles in macrophage activation, regulating the production of such cytokines as interleukin (IL)-10 and type I interferons (IFNs). Fumarate hydratase (FH) has been identified as a control point. Notably, FH loss in different models and cell types has been found to lead to DNA and RNA release from mitochondria which are sensed by cytosolic nucleic acid sensors including retinoic acid-inducible gene (RIG)-I, melanoma differentiation-associated protein (MDA)5, and cyclic GMP-AMP synthase (cGAS) to upregulate IFN-β production. These findings may have relevance in the pathogenesis and treatment of diseases associated with decreased FH levels such as systemic lupus erythematosus (SLE) or FH-deficient kidney cancer.
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