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

Year: 2007
Type: article
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.
DOI: 10.1172/jci31370
Authors: Carole Peyssonnaux, Annelies S. Zinkernagel, Reto A. Schuepbach, Erinn Rankin, Sophie Vaulont, Volker H. Haase, Victor Nizet, Randall S. Johnson
Institutions: University of California San Diego, Scripps Research Institute, University of Pennsylvania, Centre National de la Recherche Scientifique, Inserm, Institut Cochin, Université Paris Descartes
Language: English
Subfield: Hematology
Field: Medicine
Open Access status: bronze
OpenAlex ID: W2116374020
FWCI: 29.71
Cites: 36
Cited by: 641
Related to: 10