title: The regulation of cellular iron metabolism.
abstract: While iron is an essential trace element required by nearly all living organisms, deficiencies or excesses can lead to pathological conditions such as iron deficiency anemia or hemochromatosis, respectively. A decade has passed since the discovery of the hemochromatosis gene, HFE, and our understanding of hereditary hemochromatosis (HH) and iron metabolism in health and a variety of diseases has progressed considerably. Although HFE-related hemochromatosis is the most widespread, other forms of HH have subsequently been identified. These forms are not attributed to mutations in the HFE gene but rather to mutations in genes involved in the transport, storage, and regulation of iron. This review is an overview of cellular iron metabolism and regulation, describing the function of key proteins involved in these processes, with particular emphasis on the liver's role in iron homeostasis, as it is the main target of iron deposition in pathological iron overload. Current knowledge on their roles in maintaining iron homeostasis and how their dysregulation leads to the pathogenesis of HH are discussed.
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Fremantle, Western Australia, Australia.
authors.forename: Anita C G
authors.initials: AC
authors.lastname: Chua
authors.forename: Ross M
authors.initials: RM
authors.lastname: Graham
authors.forename: Debbie
authors.initials: D
authors.lastname: Trinder
authors.forename: John K
authors.initials: JK
authors.lastname: Olynyk
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000378:metabolism; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D001692:Biological Transport; D027682:Cation Transport Proteins / Q000378:metabolism; D002570:Ceruloplasmin / Q000378:metabolism; D058851:GPI-Linked Proteins; D006432:Hemochromatosis / Q000235:genetics; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption; D007501:Iron / Q000378:metabolism*; D019189:Iron Metabolism Disorders / Q000235:genetics*; D019190:Iron Overload / Q000378:metabolism; D019266:Iron, Dietary / Q000493:pharmacokinetics; D033862:Iron-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D011990:Receptors, Transferrin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D014168:Transferrin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; D002570:Ceruloplasmin; D058851:GPI-Linked Proteins; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D007501:Iron; D019266:Iron, Dietary; D033862:Iron-Binding Proteins; D008565:Membrane Proteins; D011990:Receptors, Transferrin; D014168:Transferrin; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2; C103673:HFE protein, human; C481006:HJV protein, human