Recent advance in molecular iron metabolism: translational disorders of ferritin.

Ferritin, composed of H-subunits and L-subunits, plays important roles in iron storage and in the control of intracellular iron distribution. Synthesis of both subunits is controlled by common cytoplasmic proteins, iron regulatory proteins (IRP-1 and IRP-2) that bind to the iron-responsive element (IRE) in the 5'-untranslated region of ferritin messenger RNA (mRNA). When intracellular iron is scarce, IRPs display IRE binding to suppress translation of mRNA. When cellular iron is abundant, IRPs become inactivated (IRP-1) or degraded (IRP-2). In the last few years, IRE mutations that cause disorders due to dysregulation of ferritin subunit synthesis have been identified. Hereditary hyperferritinemia-cataract syndrome is associated with point mutations or deletions in the IRE of L-subunit mRNA and is characterized by constitutively increased synthesis of L-subunits but is unrelated to iron overload. A single-point mutation in the IRE of H-subunit mRNA in members of a family affected with dominantly inherited iron overload has been reported. This review summarizes the current understanding of the translational disorders caused by IRE mutations in ferritin mRNA.