Aconitate decarboxylase 1 (ACOD1)

Aconitate decarboxylase 1 (ACOD1) is a mitochondrial enzyme, structurally a homodimer, that converts cis-aconitate (a tricarboxylic acid cycle intermediate) into itaconate, an immunomodulatory metabolite. ACOD1 is highly conserved across species and is primarily expressed in activated macrophages during infection or inflammation. Its product, itaconate, exerts broad regulatory effects on immune defenses, including inhibition of pro-inflammatory cytokines, suppression of Toll-like receptor signaling, modulation of ROS production, and alkylation (itaconation) of select proteins involved in inflammasome activation. ACOD1 is involved in both anti- and pro-inflammatory effects depending on context, and therapeutic strategies targeting the ACOD1/itaconate pathway are under investigation for infection, inflammatory, cardiovascular diseases, and metabolic disorders.

Other names

Cis-aconitate decarboxylaseCis-aconitic acid decarboxylaseImmune-responsive gene 1 proteinIRG1CADimmunoresponsive 1 homolog

Inhibitors or activators of ACOD1 typically act by modulating the production/effects of itaconate, impacting inflammatory cytokine release, ROS production, and the activity of the NLRP3 inflammasome as well as succinate dehydrogenase. Alkylation of key proteins by itaconate (itaconation), which blocks inflammasome activation and metabolic signals.