Effect of ferroportin polymorphism on iron homeostasis and infection.

Abstract

Ferroportin (FPN) is the sole iron export membrane protein identified in mammals that is abundantly expressed on absorptive enterocytes and macrophages, and is essential for physiological regulation of cellular iron. The expression of FPN is positively induced by cellular iron and is suppressed by liver hepcidin in response to either increased systemic iron or inflammatory stimuli. Hepcidin binds to cell surface FPN inducing FPN internalization followed by lysosomal degradation of the protein and consequently iron efflux from macrophages is blocked and there is suboptimal iron absorption by duodenal enterocytes. Dozens of FPN gene mutations have been identified in different ethnic populations and some of the mutations are associated with autosomal dominant iron overload disorder described as FPN disease or hemochromatosis type 4 that is distinct from hereditary hemochromatosis due to HFE mutations. Clinical manifestations of iron overload FPN disease can be classified into two groups according to whether there is selective macrophage iron loading or parenchymal and reticuloendothelial iron accumulation. There is evidence suggesting that altered hepcidin-FPN interaction can modulate host's response to infection. Resistance to hepcidin promotes iron egress from cells and this inhibits growth of intracellular pathogens. Conversely, iron retention due to loss of iron export activity by mutated FPN results in intracellular iron accumulation and a permissive environment for intracellular pathogens.

• Authors: Ishmael Kasvosve
• Journal: Clinica chimica acta; international journal of clinical chemistry (Clin Chim Acta) Vol. 416 Pg. 20-5 (Feb 01 2013) ISSN: 1873-3492 [Electronic] Netherlands
• PMID: 23178444 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Antimicrobial Cationic Peptides
• Cation Transport Proteins
• HAMP protein, human
• Hepcidins
• metal transporting protein 1

Topics

• Antimicrobial Cationic Peptides (genetics, physiology)
• Cation Transport Proteins (genetics)
• Hepcidins
• Homeostasis (genetics)
• Humans
• Polymorphism, Genetic