Aconitase 2, mitochondrial (ACO2)

Aconitase 2, mitochondrial (ACO2) is an **iron–sulfur enzyme** that catalyzes the reversible isomerization of citrate to isocitrate via cis-aconitate, constituting the second step of the tricarboxylic acid (TCA) cycle in the mitochondrial matrix[1][4]. It is encoded by the nuclear ACO2 gene and imported into mitochondria, where it supports cell energy production, iron homeostasis, and mitochondrial DNA maintenance[1][3]. The enzyme is highly sensitive to oxidative inactivation due to its [4Fe-4S] iron–sulfur cluster, making it both a target and marker of mitochondrial oxidative stress[3]. Dysfunction or mutation in ACO2 is implicated in neurodegenerative diseases and mitochondrial energy failure, and the protein’s activity is often used as a biomarker for mitochondrial redox state[3]. The only well-established drug interaction is through the toxin fluoroacetate, which is metabolized to fluorocitrate—a compound that potently inhibits aconitase enzymes, thereby arresting the TCA cycle and cellular respiration[2].

Other names

ACO2AconitaseAconitate hydratase, mitochondrialACONMCitrate hydro-lyaseICRDOCA8HEL-S-284OPA9epididymis secretory sperm binding protein Li 284

Competitive inhibition of enzyme activity (by fluorocitrate derived from fluoroacetate)[2]; Enzyme inhibition via iron–sulfur cluster oxidation/damage[3]