Emerging role of the itaconate‑mediated rescue of cellular metabolic stress

Tzu Chi Medical Journal

article

Der‑Shan Sun¹  Hsin‑Hou Chang¹ 

[1] Department of Molecular Biology and Human Genetics, Tzu Chi University

关键词: ATF3;    Inflammasome;    Itaconate;    Mitochondrial stress;    Nuclear factor erythroid 2–related factor 2;   

DOI  :  10.4103/tcmj.tcmj_79_21

来源: Wolters Kluwer Medknow Publications

【 摘 要 】

Metabolic regulations play vital roles on maintaining the homeostasis of our body. Evidence have suggested that ATF3 and nuclear factor erythroid 2–related factor 2 (NRF2) are critical for maintaining cell function, metabolism, and inflammation/anti‑inflammation regulations when cells are under stress, while the upstream regulators in the stressed cells remain elusive. Recent findings have shown that tricarboxylic acid cycle metabolites such as itaconate and succinate are not just mitochondrial metabolites, but rather important signaling mediators, involving in the regulations of metabolism, immune modulation. Itaconate exerts anti‑inflammatory role through regulating ATF3 and NRF2 pathways under stressed conditions. In addition, itaconate inhibits succinate dehydrogenase, succinate oxidation and thus blocking succinate‑mediated inflammatory processes. These findings suggest itaconate‑ATF3 and itaconate‑NRF2 axes are well‑coordinated machineries that facilitate the rescue against cellular stress. Here, we review these fascinating discoveries, a research field may help the development of more effective therapeutic approach to manage stress‑induced inflammation, tissue damage, and metabolic disorder.

【 授权许可】

Unknown