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Iron exporter revealed that may explain common human disorder

ting iron back out of cells remained indirect. To determine which cells depend on ferroportin, the researchers inactivated the protein in mice, both globally and in select tissues.

Animals completely lacking ferroportin died early in development due to a failure of iron transfer from mother to embryo. Mice deficient for ferroportin in all tissues except those critical for maternal nutrient transfer survived but quickly became anemic after birth due to iron deficiency in the blood. Examination of the animals' intestine, liver, and spleen revealed an accumulation of iron within cells, indicating an inability of cells to release iron once absorbed.

Mice lacking ferroportin only in intestinal cells also developed severe iron deficiency anemia, further confirming the protein's role in iron absorption.

The findings offer insight into the underlying basis for hemochromatosis, Andrews said. The researchers propose that, in patients with the disease, perturbations in iron homeostasis result from a failure to control iron export through ferroportin, leading to increased iron release from macrophages and enhanced intestinal absorption. Indeed, patients with the disease exhibit a deficiency of hepcidin, a hormone that binds ferroportin and targets it for destruction.

Drugs that inhibit or degrade ferroportin might therefore curb the iron overload suffered by those with hemochromatosis, Andrews said. Those with excess iron for other reasons, such as repeated blood transfusions, might also benefit from such a drug, she added.

The other members of the research team include Adriana Donovan from Children's Hospital Boston and Harvard Medical School; Christine A. Lima from Children's Hospital Boston and Howard Hughes Medical Institute; Jack L. Pinkus and Geraldine S. Pinkus from Brigham and Women's Hospital; Leonard I. Zon and Nancy C. Andrews from Children's Hospital Boston, Harvard Medical School, and Howard Hughes Medical Institute; and Sylv
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Contact: Heidi Hardman
hhardman@cell.com
1-617-397-2879
Cell Press
15-Mar-2005


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