Aconitase 1 (ACO1)

Aconitase 1 (ACO1) is a bifunctional cytosolic enzyme that acts both as an aconitase in the tricarboxylic acid (TCA) cycle and, under iron-deficient conditions, as a posttranscriptional regulator of iron metabolism by binding iron-responsive elements in mRNAs. When cellular iron is abundant, ACO1 incorporates a [4Fe-4S] cluster and catalyzes the conversion of citrate to isocitrate. When iron is scarce and the Fe-S cluster is lost, ACO1 switches to an RNA-binding form, regulating the stability and translation of mRNAs encoding key iron homeostasis proteins such as ferritin and the transferrin receptor. This dual function positions ACO1 as a critical sensor and effector in cellular iron balance, and its dysfunction is implicated in disorders of iron metabolism and some neurodegenerative diseases[1][2][3].

Other names

Iron regulatory protein 1IRP1Iron-responsive element-binding protein 1IREB1IREBPIREBP1Aconitate hydratase, cytoplasmicCytoplasmic aconitate hydrataseFerritin repressor proteinSoluble aconitaseACONSHEL60Cytosplasmic aconitase

Not classically pharmacologically targeted; mechanistic action involves inhibition or modulation of enzymatic activity or protein–RNA binding, but no drugs directly approved or standardly used to target ACO1[1][2][3].