糖酵解
半胱氨酸
生物化学
糖基化
焊剂(冶金)
蛋白质组
代谢物
醛缩酶A
谷胱甘肽
生物
新陈代谢
化学
细胞生物学
酶
有机化学
作者
Wei Qin,Ke Qin,Zhang Yan-ling,Wentong Jia,Ying Chen,Bo Cheng,Linghang Peng,Nan Chen,Yuan Liu,Wen Zhou,Yanling Wang,Xing Chen,Chu Wang
标识
DOI:10.1038/s41589-019-0323-5
摘要
Itaconate has been recently recognized as an anti-inflammatory metabolite involved in the pathogen-macrophage interface. Due to its weak electrophilicity, itaconate could modify cysteines of the protein KEAP1 and glutathione, which contribute to its anti-inflammatory effect. However, the substrates of itaconate modification in macrophages have not been systematically profiled, which largely impedes the understanding of its roles in immune responses. Here, we developed a specific thiol-reactive probe, 1-OH-Az, for quantitative chemoproteomic profiling of cysteine modifications by itaconate, and provided a global portrait of its proteome reactivity. We found that itaconate covalently modifies key glycolytic enzymes and impairs glycolytic flux mainly through inhibition of fructose-bisphosphate aldolase A (ALDOA). Moreover, itaconate attenuates the inflammatory response in stimulated macrophages by impairing the glycolysis. Our study provides a valuable resource of protein targets of itaconate in macrophages and establishes a negative-feedback link between glycolysis and itaconate, elucidating new functional insights for this anti-inflammatory metabolite.
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