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Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs)


Peyssonnaux, Carole; Zinkernagel, Annelies S; Schuepbach, Reto A; Rankin, Erinn; Vaulont, Sophie; Haase, Volker H; Nizet, Victor; Johnson, Randall S (2007). Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs). The Journal of clinical investigation, 117(7):1926-1932.

Abstract

Iron is essential for many biological processes, including oxygen delivery, and its supply is tightly regulated. Hepcidin, a small peptide synthesized in the liver, is a key regulator of iron absorption and homeostasis in mammals. Hepcidin production is increased by iron overload and decreased by anemia and hypoxia; but the molecular mechanisms that govern the hepcidin response to these stimuli are not known. Here we establish that the von Hippel-Lindau/hypoxia-inducible transcription factor (VHL/HIF) pathway is an essential link between iron homeostasis and hepcidin regulation in vivo. Through coordinate downregulation of hepcidin and upregulation of erythropoietin and ferroportin, the VHL-HIF pathway mobilizes iron to support erythrocyte production.

Abstract

Iron is essential for many biological processes, including oxygen delivery, and its supply is tightly regulated. Hepcidin, a small peptide synthesized in the liver, is a key regulator of iron absorption and homeostasis in mammals. Hepcidin production is increased by iron overload and decreased by anemia and hypoxia; but the molecular mechanisms that govern the hepcidin response to these stimuli are not known. Here we establish that the von Hippel-Lindau/hypoxia-inducible transcription factor (VHL/HIF) pathway is an essential link between iron homeostasis and hepcidin regulation in vivo. Through coordinate downregulation of hepcidin and upregulation of erythropoietin and ferroportin, the VHL-HIF pathway mobilizes iron to support erythrocyte production.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Division of Surgical Intensive Care Medicine
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2007
Deposited On:11 Dec 2012 17:52
Last Modified:05 Apr 2016 16:09
Publisher:American Society for Clinical Investigation
Series Name:Journal of Clinical Investigation
ISSN:0021-9738
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1172/JCI31370
PubMed ID:17557118

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