Molecular mechanisms of normal iron homeostasis.
Humans possess elegant control mechanisms to maintain iron homeostasis by coordinately regulating iron absorption, iron recycling, and mobilization of stored iron. Dietary iron absorption is regulated locally by hypoxia inducible factor (HIF) signaling and iron-regulatory proteins (IRPs) in enterocytes and systematically by hepatic hepcidin, the central iron regulatory hormone. Hepcidin not only controls the rate of iron absorption but also determines iron mobilization from stores through negatively modulating the function of ferroportin, the only identified cellular iron exporter to date. The regulation of hepatic hepcidin is accomplished by the coordinated activity of multiple proteins through different signaling pathways. Recent studies have greatly expanded the knowledge in the understanding of hepcidin expression and regulation by the bone morphogenetic protein (BMP) signaling, the erythroid factors, and inflammation. In this review, we mainly focus on the roles of recently identified proteins in the regulation of iron homeostasis.
Zhang
An-Sheng
AS
Oregon Health & Science University, Portland, OR 97239, USA.
Enns
Caroline A
CA
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D027682:Cation Transport Proteins / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D051793:Hypoxia-Inducible Factor 1 / Q000502:physiology; D007249:Inflammation / Q000378:metabolism; D007408:Intestinal Absorption; D007501:Iron / Q000378:metabolism*; D019266:Iron, Dietary / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D014168:Transferrin / Q000378:metabolism; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
D023181:Antimicrobial Cationic Peptides; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D051793:Hypoxia-Inducible Factor 1; D007501:Iron; D019266:Iron, Dietary; D008565:Membrane Proteins; D014168:Transferrin; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2; C578702:HAMP protein, human; C103673:HFE protein, human; C579599:Hamp protein, mouse