Regulation of the Hif2α subunit in the kidney. Translational regulation: Binding of IRP1 to the 5’ RNA stem-loop of Hif2α inhibits its translation. The conformational change of IRP1 between its RNA-binding form (IRP1) and its cytosolic Aco1 form is an iron-sensing mechanism that functions only in the presence of sufficient oxygen or reactive oxygen/nitrogen species. The steep oxygen gradient in the kidney suggests that the regulatory range of IRP1 may vary depending on its specific location within the tissue. Degradational regulation: All 3 Hifα subunits undergo degradational regulation by prolyl hydroxylases (PHDs), which are activated in the presence of oxygen and iron. HRE, hypoxia-responsive element; UTR, untranslated region. Professional illustration by Patrick Lane, ScEYEnce Studios.