IRE‐dependent Regulation of Intestinal Dmt1 Prevails During Chronic Dietary Iron Deficiency but is Dispensable in Conditions of Acute Erythropoietic Stress

Iron must be supplied in adequate amounts to sustain erythropoiesis while avoiding toxic iron accumulation.1 Whole body iron levels are largely determined by the rate of dietary iron absorption in the duodenum.2 Divalent metal transporter 1 (DMT1, encoded by Slc11a2) is an essential iron transporter present at the apical membrane of absorptive enterocytes.3 It mediates the influx of nonheme iron from the intestinal lumen into the interior of the cell after reduction of the metal by CYBRD1 (a.k.a. DCYTB); iron is then either stored intracellularly into nanocages made of ferritin-H (FTH1) and -L (FTL1) subunits, or exported into the circulation by the basolaterally expressed transporter ferroportin (FPN, a.k.a. SLC40A11) to be loaded onto transferrin after oxidation of the metal by hephaestin (HEPH).4