Stabilization of iron regulatory protein 2, IRP2, by aluminum

Iron regulatory protein 2 (IRP2) is one of the central regulators of iron homeostasis. IRP2 regulates expression of molecules involved in iron metabolism by binding to iron responsive elements (IREs) in the transcripts of those molecules in iron depletion. IRP2 is regulated by the accelerated degradation initiated by the iron-catalyzed oxidation. Here we report that aluminum antagonizes the iron-induced decrease in IRE binding activity of IRP2. Aluminum also inhibits iron-induced oxidation of IRP2 in vitro. These results suggest that aluminum stabilizes IRP2 by interfering with the iron-catalyzed oxidation, which results in perturbation of iron metabolism.