Internal medicine

Downregulation and upregulation

Organic chemistry

Transcription factor

Biology

Gene

Endocrinology

Hypoxia-inducible factors

Chemistry

Immunology

Anemia

Ferroportin

Hepcidin

Inflammation

Erythropoietin

Erythropoiesis

Regulator

Cell biology

Oxygen

Biochemistry

Homeostasis

Medicine

Hypoxia (environmental)

Journal of Clinical Investigation

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.

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