Donovan, A. et al. The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis. Cell Metab. 1, 191-200

Children's Hospital Boston, Boston, Massachusetts 02115, USA.
Cell Metabolism (Impact Factor: 16.75). 04/2005; 1(3):191-200. DOI: 10.1016/j.cmet.2005.01.003
Source: PubMed

ABSTRACT Ferroportin (SLC40A1) is an iron transporter postulated to play roles in intestinal iron absorption and cellular iron release. Hepcidin, a regulatory peptide, binds to ferroportin and causes it to be internalized and degraded. If ferroportin is the major cellular iron exporter, ineffective hepcidin function could explain manifestations of human hemochromatosis disorders. To investigate this, we inactivated the murine ferroportin (Fpn) gene globally and selectively. Embryonic lethality of Fpn(null/null) animals indicated that ferroportin is essential early in development. Rescue of embryonic lethality through selective inactivation of ferroportin in the embryo proper suggested that ferroportin has an important function in the extraembryonic visceral endoderm. Ferroportin-deficient animals accumulated iron in enterocytes, macrophages, and hepatocytes, consistent with a key role for ferroportin in those cell types. Intestine-specific inactivation of ferroportin confirmed that it is critical for intestinal iron absorption. These observations define the major sites of ferroportin activity and give insight into hemochromatosis.

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Available from: Sylvie Robine, Oct 21, 2014
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    • "Lastly, differences in mouse strains could underlie the difference in phenotypes. Lakhal- Littleton et al. used C57BL6 mice to generate their conditional knockout mice, whereas our Fpn-floxed mice were maintained on the 129/ SvEvTac background [5]. Notably, Lakhal-Littleton et al. purchased their ES cells from the European Mouse Mutant Cell Consortium, which commonly uses the gene-trap approach for targeting. "
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    • "It is the only known mammalian Fe export protein that is responsible for the movement of Fe from the enterocytes into the circulation. Deletion of FPN1 in intestinal cells in mice results in a near complete block of intestinal Fe absorption and a consequent accumulation of Fe in intestinal enterocytes (Donovan et al., 2005). FPN1 transports Fe in the ferrous form, while plasma "
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    • "Ps , and repressed by anemia and hypoxia ( Andriopoulos et al . , 2009 ; Ganz , 2004 ; Ganz and Nemeth , 2012 ; Nemeth et al . , 2004a ) . Hepcidin is the only known master hormone modulating systemic iron homeostasis , and ferroportin is its receptor , an iron exporter found in duodenal enterocytes , macrophages , osteo - clasts and hepatocytes ( Donovan et al . , 2005 ) . Upon binding to hepcidin , ferroportin is internalized and degraded via ubiquitin - dependent proteasomal degradation , leading to decreased iron egress from the above mentioned cells ( Nemeth et al . , 2004b ) . Hepcidin defect leads to iron retention in macrophages , hepatocytes and osteoclasts . Our own re - cent results suggeste"
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