Ferroportin

Ferroportin is a transmembrane protein that transports iron from the inside of a cell to the outside of it. It is found on the surface of cells that store or transport iron, including:

• Enterocytes in the duodenum
• Hepatocytes
• Macrophages of the reticuloendothelial system.

Role in iron metabolism

Recent research suggests that ferroportin is inhibited by hepcidin, which binds to ferroportin and internalises it within the cell. This results in the retention of iron within cells, and a reduction in iron levels within the plasma. This is especially significant in enterocytes which are shed at the end of their lifespan. The extra iron retained within them is not only prevented from entering the bloodstream but ends up being excreted into the faeces. Hepcidin is thus the "master regulator" of human iron metabolism.

This is part of the mechanism that causes anaemia of chronic disease; hepcidin is released from the liver in response to inflammatory cytokines, namely interleukin-6, which results in an increased hepcidin concentration and a consequent decrease in plasma iron levels.

Clinical significance

Mutations in the ferroportin gene are known to cause an autosomal dominant form of iron overload known as Type IV Haemochromatosis or Ferroportin Disease. The effects of the mutations are generally not severe but a spectrum of clinical outcomes are seen with different mutations. Ferroportin is also associated with African iron overload. Ferroportin and hepcidin are critical proteins for the regulation of systemic iron homeostasis. Both ferroportin and hepcidin are expressed in cultured human breast epithelial cells and hepcidin regulates ferroportin in these cells. Transfection of breast cancer cells with ferroportin significantly reduces their growth after orthotopic implantation in the mouse mammary fat pad. Ferroportin is a pivotal protein in breast biology and a strong and independent predictor of prognosis in breast cancer.^[1]

References

Further reading

External links

• MeSH ferroportin1+protein