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: 17.57). 04/2005; 1(3):191-200. DOI: 10.1016/j.cmet.2005.01.003
Source: PubMed


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.

Download full-text


Available from: Sylvie Robine, Oct 21, 2014
  • Source
    • "Type IV HH (ferroportin disease) differs from the other ones for having an autosomal dominant transmission and for not affecting hepcidin expression. It is caused by mutations in the SLC40A gene, which encodes the Fe exporter Fpn, namely the hepcidin target[43]. Known also as ferroportin disease, this is characterized by hyperferritinaemia, normal Tf saturation, and Fe-loaded macrophages[44]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Iron is required for the survival of most organisms, including bacteria, plants, and humans. Its homeostasis in mammals must be fine-tuned to avoid iron deficiency with a reduced oxygen transport and diminished activity of Fe-dependent enzymes, and also iron excess that may catalyze the formation of highly reactive hydroxyl radicals, oxidative stress, and programmed cell death. The advance in understanding the main players and mechanisms involved in iron regulation significantly improved since the discovery of genes responsible for hemochromatosis, the IRE/IRPs machinery, and the hepcidin-ferroportin axis. This review provides an update on the molecular mechanisms regulating cellular and systemic Fe homeostasis and their roles in pathophysiologic conditions that involve alterations of iron metabolism, and provides novel therapeutic strategies to prevent the deleterious effect of its deficiency/overload.
    Full-text · Article · Jan 2016 · International Journal of Molecular Sciences
  • Source
    • "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. "

    Full-text · Article · Jul 2015 · International Journal of Cardiology
  • Source
    • "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 "

    Full-text · Article · Jul 2015 · Critical reviews in food science and nutrition
Show more