Figure 1.

Iron absorption and homeostasis: The dietary non-heme iron is first reduced to ferrous form by Dcytb and is taken up via DMT1 at the apical surface of the enterocytes. Dietary heme iron is taken up via HCP 1 and degraded inside the cell by HO-1 to release iron. Within the enterocyte, the iron is either stored in ferritin or transported to the circulation. At the basolateral membrane, the ferrous iron transported via FPN1, coupled with its oxidation by HEPH. The senescent erythrocytes are phagocytosed by macrophages via CD91/CD163, and are degraded in lysosomal compartments to release iron, which then are excreted into cytosol via DMT1. The iron is then transported out of the macrophage via FPN1 possibly coupled with ceruloplasmin dependent iron oxidation. In the blood, ferric iron is transported bound to Tf, and delivered to the target tissues, the bone marrow, liver and muscle via TfR-dependent mediated endocytosis pathway. When the iron stores are adequate, the hepcidin released from the liver into the blood, which in turn inhibits the FPN1 mediated iron release from intestinal cells and other tissues involved in iron mobilization.