The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Donovan, A; Lima, CA; Pinkus, JL; Pinkus, GS; Zon, LI; Robine, S; Andrews, NC

Published Date

  • March 2005

Published In

Volume / Issue

  • 1 / 3

Start / End Page

  • 191 - 200

PubMed ID

  • 16054062

Pubmed Central ID

  • 16054062

International Standard Serial Number (ISSN)

  • 1550-4131

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2005.01.003

Language

  • eng

Conference Location

  • United States