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5 Iron uptake by hepatocytes. (1) TFR1 pathway: Diferric TF binds to TFR1 and is endocytosed into endosomes. Acidified endosome releases iron via DMT1 after being reduced to Fe 2+ by STEAP3. Apo TF is recycled. (2) TFR2 pathway: similar to the TFR1 pathway. (3) NTBI uptake: Iron is reduced by ferrireductase and transported inside the cytosol by the iron carrier. (4) Ferritin uptake: Ferritin is endocytosed after binding to its membrane receptor. The endosome is then transferred to the lysosomal compartment and iron is then either directed to intracellular ferritin or to the transient iron pool. (5) Uptake of haem-haemopexin and haemoglobin-haptoglobin complexes: Complexes bind their receptors (CD91 for haem-haemopexin and CD163 for haemoglobin-haptoglobin) and are endocytosed and moved to lysosomes. Haem is then removed and oxidised by HO1 and moved to transient iron pool. (6) Hepatic iron efflux: Iron is released from the hepatocytes by IREG1 and oxidised by Cp before binding to TF. Modified from (Chua et al. 2007).
Source publication
Hepcidin is the key regulator of iron homeostasis acting as a negative regulator of intestinal iron absorption. Several proteins have recently been identified to act as upstream regulators of hepcidin expression, such as HFE and hemojuvelin (HJV). Although hepcidin is regulated by iron, the molecules involved in this regulation and whether HFE is i...
