Iron transport across cell membranes: molecular understanding of duodenal and placental iron uptake

Iron is an essential element playing a vital role in many cellular processes. This requirement is complicated by the fact that environmental iron is invariably present as insoluble Fe3+ leading to poor bioavailability and toxicity, since even low concentrations of iron catalyse the production of damaging reactive oxygen species. As a result organisms have evolved efficient uptake and transport systems to extract iron from their environment as well as ferritins that store iron in a non-toxic form. In higher organisms, the first membrane barrier encountered is the apical surface of the duodenal enterocyte, a specialized absorptive cell of the intestinal epithelium that undertakes vectorial transport of iron. Iron is initially solubilized by reduction and Fe2+ is transported across the cell membrane by a carrier-mediated transport process. This is followed by intracellular transfer of iron to the basolateral enterocyte membrane with subsequent transfer and release of iron to transferrin in the portal blood. A second site of iron transport is at the placento–fetal barrier where similar principles operate. In this review we describe recently identified transmembrane transporters and associated accessory proteins responsible for iron transport at these two sites.