Reactome | ACO1 binds 4Fe-4S

ACO1 binds 4Fe-4S

Stable Identifier

R-HSA-5690873

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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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).

Literature References

PubMed ID	Title	Journal	Year
16407072	Crystal structure of human iron regulatory protein 1 as cytosolic aconitase Dupuy, J, Volbeda, A, Carpentier, P, Darnault, C, Moulis, JM, Fontecilla-Camps, JC	Structure	2006
1946430	A regulated RNA binding protein also possesses aconitase activity Kaptain, S, Downey, WE, Tang, C, Philpott, C, Haile, D, Orloff, DG, Harford, JB, Rouault, TA, Klausner, RD	Proc. Natl. Acad. Sci. U.S.A.	1991
8041788	The bifunctional iron-responsive element binding protein/cytosolic aconitase: the role of active-site residues in ligand binding and regulation Philpott, CC, Klausner, RD, Rouault, TA	Proc. Natl. Acad. Sci. U.S.A.	1994