Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization.
Hepcidin is a peptide hormone secreted by the liver in response to iron loading and inflammation. Decreased hepcidin leads to tissue iron overload, whereas hepcidin overproduction leads to hypoferremia and the anemia of inflammation. Ferroportin is an iron exporter present on the surface of absorptive enterocytes, macrophages, hepatocytes, and placental cells. Here we report that hepcidin bound to ferroportin in tissue culture cells. After binding, ferroportin was internalized and degraded, leading to decreased export of cellular iron. The posttranslational regulation of ferroportin by hepcidin may thus complete a homeostatic loop: Iron regulates the secretion of hepcidin, which in turn controls the concentration of ferroportin on the cell surface.
Nemeth
Elizabeta
E
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Tuttle
Marie S
MS
Powelson
Julie
J
Vaughn
Michael B
MB
Donovan
Adriana
A
Ward
Diane McVey
DM
Ganz
Tomas
T
Kaplan
Jerry
J
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D001692:Biological Transport; D027682:Cation Transport Proteins / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005293:Ferritins / Q000378:metabolism; D006367:HeLa Cells; D064451:Hepcidins; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D035942:Iron Regulatory Protein 2 / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D014168:Transferrin / Q000378:metabolism; D000098742:Ferroportin
D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; C578702:HAMP protein, human; C579599:Hamp protein, mouse; D064451:Hepcidins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014168:Transferrin; D000098742:Ferroportin; D005293:Ferritins; D007501:Iron; D066246:ErbB Receptors; D035942:Iron Regulatory Protein 2