Physiology of iron transport and the hemochromatosis gene.
Iron is essential for fundamental cell functions but is also a catalyst for chemical reactions involving free radical formation, potentially leading to oxidative stress and cell damage. Cellular iron levels are therefore carefully regulated to maintain an adequate substrate while also minimizing the pool of potentially toxic "free iron." The main control of body iron homeostasis in higher organisms is placed in the duodenum, where dietary iron is absorbed, whereas no controlled means of eliminating unwanted iron have evolved in mammals. Hereditary hemochromatosis, the prototype of deregulated iron homeostasis in humans, is due to inappropriately increased iron absorption and is commonly associated to a mutated HFE gene. The HFE protein is homologous to major histocompatibility complex class I proteins but is not an iron carrier, whereas biochemical and cell biological studies have shown that the transferrin receptor, the main protein devoted to cellular uptake of transferrin iron, interacts with HFE. This review focuses on recent advances in iron research and presents a model of HFE function in iron metabolism.
Pietrangelo
Antonello
A
Unit for the Study of Iron Metabolism, University of Modena and Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy. pietrangelo.antonello@unimo.it
D000818:Animals; D001692:Biological Transport; D004032:Diet; D006680:HLA Antigens / Q000235:genetics; D006432:Hemochromatosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D006454:Hemoglobins / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D007408:Intestinal Absorption; D007501:Iron / Q000008:administration & dosage / Q000378:metabolism*; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D008565:Membrane Proteins; D009154:Mutation; D011990:Receptors, Transferrin / Q000235:genetics / Q000502:physiology; D014168:Transferrin / Q000378:metabolism
C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D006454:Hemoglobins; D015395:Histocompatibility Antigens Class I; D007506:Iron-Sulfur Proteins; D008565:Membrane Proteins; D011990:Receptors, Transferrin; D014168:Transferrin; D007501:Iron