Ferroportin is a multipass membrane protein that serves as an iron exporter in many vertebrate cell types. Ferroportin-mediated iron export is controlled by the hormone hepcidin, which binds ferroportin, causing its internalization and degradation. Mutations in ferroportin cause a form of the iron overload hereditary disease hemochromatosis. Relatively little is known about ferroportin's proper...

In vertebrates, the iron exporter ferroportin releases Fe(2+) from cells into plasma, thereby maintaining iron homeostasis. The transport activity of ferroportin is suppressed by the peptide hormone hepcidin, which exhibits upregulated expression in chronic inflammation, causing iron-restrictive anaemia. However, due to the lack of structural information about ferroportin, the mechanisms of its...

Hepcidin is a peptide hormone secreted by the liver in response to iron loading and inflammation. Decreased hepcidin leads to tissue iron overload, whereas hepcidin overproduction leads to hypoferremia and the anemia of inflammation. Ferroportin is an iron exporter present on the surface of absorptive enterocytes, macrophages, hepatocytes, and placental cells. Here we report that hepcidin bound...

BACKGROUND Absorption of non-haeme iron occurs mainly in the duodenum. It involves the divalent metal transporter 1 (DMT1) in the uptake of ferrous Fe(II) iron and the basolateral transporter ferroportin/IREG-1/MTP-1/SLC40A1 in its release. Whether ferroportin functions in this process at other sites in the enterocyte is unknown. In this study the effect of a blocking antibody to ferroportin on...

BACKGROUND & AIMS Previous studies have suggested that iron absorption in suckling mammals is refractory to stimuli that normally would decrease absorption in adults. To better understand the regulation of iron absorption during suckling, we have characterized the relationship between hepcidin, ferroportin, and iron absorption at this crucial stage of life. METHODS To determine whether ferrop...

ciency or ferroportin Q248H had lower circulating tumor necrosis factor-α concentrations than iron-replete children with WT ferroportin, led us to hypothesize that ferroportin Q248H has reduced sensitivity to hepcidin but that this property would be observed at lower concentrations of hepcidin than those used in previous studies. Here, we analyzed the sensitivity of ferroportin Q248H to hepcidi...

Intestinal epithelial cells and reticuloendothelial macrophages are, respectively, involved in diet iron absorption and heme iron recycling from senescent erythrocytes, two critical processes of iron homeostasis. These cells appear to use the same transporter, ferroportin (Slc40a1), to export iron. The aim of this study was to compare the localization, expression, and regulation of ferroportin ...

Iron homeostasis is achieved by regulating the intestinal absorption of the metal and its recycling by macrophages. Iron export from enterocytes or macrophages to blood plasma is thought to be mediated by ferroportin under the control of hepcidin. Although ferroportin was identified over a decade ago, little is understood about how it works. We expressed in Xenopus oocytes a human ferroportin-e...

Systemic iron levels must be maintained in physiological concentrations to prevent diseases associated with iron deficiency or iron overload. A key role in this process plays ferroportin, the only known mammalian transmembrane iron exporter, which releases iron from duodenal enterocytes, hepatocytes, or iron-recycling macrophages into the blood stream. Ferroportin expression is tightly controll...

BACKGROUND & AIMS Classical ferroportin disease is characterized by hyperferritinemia, normal transferrin saturation, and iron overload in macrophages. A non-classical form is characterized by additional hepatocellular iron deposits and a high transferrin saturation. Both forms demonstrate autosomal dominant transmission and are associated with ferroportin gene (SLC40A1) mutations. SLC40A1 enco...