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.
Kato
Junji
J
Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan. jkato@sapmed.ac.jp
Niitsu
Yoshiro
Y
D002386:Cataract; D005293:Ferritins / Q000235:genetics* / Q000378:metabolism*; D016368:Frameshift Mutation; D006801:Humans; D019190:Iron Overload / Q000235:genetics* / Q000503:physiopathology; D035925:Iron-Regulatory Proteins / Q000235:genetics* / Q000494:pharmacology; D017354:Point Mutation; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D013577:Syndrome
D035925:Iron-Regulatory Proteins; D012333:RNA, Messenger; D005293:Ferritins