Ferreting out a possible way to inhibit ferritin processing and prevent iron overload
Research in mice suggests it may one day be possible to treat hemochromatosis by inhibiting a protein that can contribute to the overabsorption of iron. The body responds to iron deficiency by absorbing iron through the small intestine. The intestinal cells protect themselves from potentially toxic iron levels by packaging the absorbed iron into a protein complex called ferritin. As needed, the cells process the ferritin and release iron into the bloodstream. The body responds to sufficient iron levels by inhibiting this process to help avoid a potentially toxic iron glut. Unfortunately, this inhibitory system sometimes goes awry, allowing the body to absorb and release too much iron, a dangerous condition known as hemochromatosis.
Research has now illuminated new details on the process of ferritin processing, revealing a potentially beneficial approach to treating hemochromatosis. Scientists identified a protein known as NCOA4 that plays a key role in processing ferritin to allow release of iron in the blood. In mice with a version of hemochromatosis, eliminating the protein from intestinal cells protected the animals from iron overload, while still allowing sufficient iron absorption to meet their needs. If the process is found to work the same way in people, and if a safe and effective way to control NCOA4 in the intestine can be identified, it may one day provide an effective means for treating hemochromatosis to people with the disease.
Das NK, Jain C, Sankar A,...Shah YM. Modulation of the HIF2α-NCOA4 axis in enterocytes attenuates iron loading in a mouse model of hemochromatosis. Blood 139: 2547-2552, 2022.