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, 1 (3), 191-200

The Iron Exporter ferroportin/Slc40a1 Is Essential for Iron Homeostasis

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The Iron Exporter ferroportin/Slc40a1 Is Essential for Iron Homeostasis

Adriana Donovan et al. Cell Metab.

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.

Comment in

  • Cellular Iron: Ferroportin Is the Only Way Out
    T Ganz. Cell Metab 1 (3), 155-7. PMID 16054057. - Review
    Ferroportin is the sole cellular efflux channel for iron and is regulated by the iron regulatory hormone hepcidin, which binds ferroportin and induces its internalization …

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