Iron and citrate are essential for the metabolism of most organisms so their regulation is critical for normal physiology and survival. Depending on cellular conditions, cytoplasmic aconitate hydratase (ACO1 aka iron regulatory protein 1, IRP1) can assume two different functions. During iron scarcity or oxidative stress, ACO1 functions as IRP1, binding to iron responsive elements (IREs) to modulate the translation of iron metabolism genes. In iron-rich conditions, IRP1 binds an iron-sulfur cluster (4Fe-4S) to function as a cytosolic aconitase. This functional duality of IRP1 connects the translational control of iron metabolising proteins to cellular iron levels.Under iron-replete conditions, ACO1 binds the cofactor 4Fe-4S cluster and acts as an aconitase, isomerising citrate (CIT) to isocitrate (ISCIT) (Kaptain et al. 1991, Philpott et al. 1994, Dupuy et al. 2006).
Kaptain, S, Downey, WE, Tang, C, Philpott, C, Haile, D, Orloff, DG, Harford, JB, Rouault, TA, Klausner, RD
Dupuy, J, Volbeda, A, Carpentier, P, Darnault, C, Moulis, JM, Fontecilla-Camps, JC
Philpott, CC, Klausner, RD, Rouault, TA
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