itaconic acid

Itaconic acid (also known as itaconate) is an endogenous dicarboxylic acid and immunometabolite produced in the mitochondria of activated macrophages via the decarboxylation of cis-aconitate, a reaction catalyzed by cis-aconitate decarboxylase (ACOD1, also known as IRG1). Itaconic acid plays a critical role in immunometabolism, linking metabolic reprogramming to the regulation of inflammation and host defense. It exerts anti-inflammatory, antioxidant, and antimicrobial effects through multiple molecular mechanisms, including the competitive inhibition of succinate dehydrogenase (SDH), the covalent alkylation of Kelch-like ECH-associated protein 1 (KEAP1) to activate the Nrf2 antioxidant pathway, and the alkylation of NLRP3 to inhibit inflammasome activation. Additionally, itaconic acid directly inhibits bacterial and fungal isocitrate lyase (ICL), a key enzyme of the glyoxylate shunt, thereby restricting the growth of pathogens such as Mycobacterium tuberculosis, Salmonella enterica, and Cryptococcus neoformans. Itaconic acid is also a competitive inhibitor of the RNA demethylase ALKBH5, which suppresses endogenous retrovirus (ERV) reactivation. It is currently under preclinical investigation by various academic institutions for the treatment of acute graft-versus-host disease (aGVHD), chronic inflammatory conditions, and infectious diseases.

Other names

1-propene-2,3-dicarboxylic acid2-methylenesuccinic acid2-methylidenebutanedioic aciditaconatemethylenesuccinic acidmethylidenebutanedioic acid