The "anemic" enterocyte in hereditary hemochromatosis: molecular insights into the control of intestinal iron absorption.

Studies of the molecular function of HFE, the protein defective in hereditary hemochromatosis, have provided important insights into the control of intestinal iron absorption. A recent study suggests that HFE controls the recycling rate of the transferrin receptor and thereby ultimately controls the iron status of the enterocyte. In hereditary hemochromatosis, a defect in HFE causes relative iron starvation in the enterocyte leading paradoxically to the development of an "anemic" enterocyte phenotype in the midst of bountiful body iron stores. Despite ever-increasing stores of body iron, the inappropriately low iron status of the hereditary hemochromatosis enterocyte continues to drive the hyper-absorption of dietary iron, eventually leading to iron overload.