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Iron exporter revealed that may explain common human disorder

The first direct evidence that a single protein is critical in the cellular export of iron may help to explain human hemochromatosis, researchers report in the March issue of Cell Metabolism.

Hemochromatosis--which affects one in every 200 to 300 people in Western populations --causes tissues of the body to become overloaded with iron. Left untreated, the hereditary disease can lead to organ failure.

The new work, led by researchers at the Children's Hospital Boston and Harvard Medical School, finds that the protein ferroportin is the major, if not the only, iron exporter that functions in key sites of iron absorption and release in the body. The findings suggest that the iron accumulation seen in those with hemochromatosis may stem from a loss of control over iron export through ferroportin, the researchers said.

"Iron is essential in the body and abundant in the environment, but it's also very reactive and damaging when in excess," said Nancy Andrews, senior author of the study. "Mammals have therefore evolved mechanisms to get enough iron from the diet, but not too much."

Iron is an essential ingredient of hemoglobin, the protein molecule in red blood cells that carries oxygen from the lungs to the body's tissues. Unlike other metals, iron cannot be eliminated through the liver or kidneys, Andrews explained. Iron balance is maintained instead through the complex regulation of tissues that transport, store, and utilize iron.

Mammals, including humans, initially obtain iron from their mothers. After birth, the intestine absorbs dietary iron and releases it into the bloodstream where developing red blood cells incorporate the iron into hemoglobin. When red blood cells die, macrophage cells consume them and recycle the iron they contain. Macrophages and liver cells also store any excess iron.

Earlier work had identified a single protein that imports iron into cells. However, the evidence for ferroportin's role in expor
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Contact: Heidi Hardman
hhardman@cell.com
1-617-397-2879
Cell Press
15-Mar-2005


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