Cells Pumping Iron

Scientists have known for decades that the human body requires iron to function properly. But exactly how this crucial nutrient gets from food into the body has been a long-standing mystery. Now, in article to be published later this week in Nature, researchers appears to have identified a protein that carries iron and many other metals into cells. Experts say the finding may hold the key to developing ways to treat patients with iron deficiency or iron overload--both dangerous conditions.

Iron is required to make hemoglobin, the protein that carries oxygen throughout the body, as well as for a variety of essential biological processes. However, regardless of the amount of iron-containing food some people eat, they cannot take in enough iron and, thus, become chronically anemic. Other people, who suffer from what's called idiopathic hemochromatosis, take in too much iron--which damages the heart, liver, and joints. Effective therapies for either group of patients have proven elusive because the mechanism by which iron moves into the body has been unclear.

To look for a possible protein responsible for transporting iron across cell membranes, postdoctoral researcher Hiromi Gunshin and colleagues at Brigham and Women's Hospital in Boston began by feeding rats a low-iron diet. The deficiency, they reasoned, would cause the rats to make more of the putative iron-transport protein, making it easier to find. They then purified messenger RNA--a molecule that plays a key role in the production of proteins--from the cells in the animals' upper intestines, injected the mRNA into immature eggs cells, and looked for changes in iron uptake. After seeing an initial sevenfold increase, they further purified the mRNA and found a protein, which they named DCT1, that boosted iron uptake 200-fold. DCT1 also changed the so-called inward current of the cells, indicating a better ability to pull metal ions--including other essential minerals such as zinc, manganese, and copper--across the membrane.

Further experiments indicated that DCT1 is important in iron transport in adult rats. When the researchers tested tissues of rats with induced iron deficiency for the presence of DCT1, they found levels dramatically higher in the intestine--the primary site where the body absorbs iron. Gunshin speculates that rats' tissues significantly increased amounts of DCT1 to try to maintain normal iron levels.

The finding makes a "compelling case" for DCT1's role as an iron transporter, says Harvard Medical School's Nancy Andrews, who today published similar results in Nature Medicine based on anemic mice. The two papers, she says, make a "nice complement."

Posted in Biology