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 Fe(3+) 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 Fe(2+) 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.