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. 2019 Jan 1;12(1):5. doi: 10.3390/ph12010005

Figure 3.

Figure 3

Cellular iron homeostasis: iron responsive element (IRE)/ iron regulatory protein (IRP) system. IRP1 and IRP2 bind to IREs present in either the 5’ untranslated regions (UTR) or 3’ UTR of mRNAs and regulate their translation and stability, respectively. In iron-depleted cells, IRPs bind to an IRE localized in the 5’ UTR of mRNAs to repress translation, while IRP binding to IREs in the 3’ UTR stabilizes mRNAs. In iron-replete cells, IRP1 switches from its IRE-binding form to a Fe-S cluster containing aconitase and IRP2 is degraded. The lack of IRP binding to IREs allows for the translation of mRNAs containing an IRE in the 5’ UTR and degradation of mRNAs containing IREs in the 3’ UTR. This mechanism counterbalances both cellular iron deficiency and iron overload. (Fpn—ferroportin; FtL—ferritin light chain; FtH—ferritin heavy chain; HIF-2α—hypoxia-inducible factor-2α).