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

C Peyssonnaux, AS Zinkernagel… - The Journal of …, 2007 - Am Soc Clin Investig
C Peyssonnaux, AS Zinkernagel, RA Schuepbach, E Rankin, S Vaulont, VH Haase, V Nizet
The Journal of clinical investigation, 2007Am Soc Clin Investig
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 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.
The Journal of Clinical Investigation