Fig. 1.

Regulation of iron homeostasis in mammals. Iron (Fe) derived either from the destruction of red blood cells (RBC) or from dietary sources in the intestine is transported into the cytosol of macrophages and enterocytes, respectively, via the transporter Nramp2. The metal can be used for cellular metabolism, stored in complex with ferritin, or exported by FPN into the circulation, where it binds to Tf. The hepatocyte-derived peptide hepcidin, the expression of which is upregulated by iron overload and inflammation and downregulated by iron deficiency, anemia and hypoxia, plays a central role in iron homeostasis by binding to FPN and inducing its internalization and degradation.