Iron homeostasis system

The iron homeostasis system is a tightly regulated physiological network responsible for the absorption, transport, and storage of iron to meet metabolic demands while preventing cellular toxicity (NIH StatPearls). Dietary iron is primarily absorbed in the duodenum via divalent metal transporter 1 (DMT1) for non-heme iron and specialized pathways for heme iron (PubMed PMID: 25151561). Once internalized by enterocytes, iron is either sequestered in ferritin for storage or exported into the systemic circulation through ferroportin, the only known mammalian iron exporter (UniProt Q9NP59). Systemic iron levels are primarily controlled by the liver-secreted hormone hepcidin, which induces the degradation of ferroportin to limit iron entry into the plasma (Nature Reviews Drug Discovery). In the blood, iron is safely transported bound to transferrin and delivered to cells, particularly erythroid precursors, via transferrin receptor 1 (TfR1) mediated endocytosis (UniProt P02786). Dysregulation of this system can lead to iron deficiency anemia or iron overload disorders such as hereditary hemochromatosis (NIH StatPearls). Therapeutic strategies include iron supplementation for deficiency, iron chelators for overload, and emerging hepcidin-targeted therapies for managing iron-restricted anemias and polycythemia (Nature Reviews Drug Discovery).

Other names

Iron metabolismIron homeostasisIntestinal iron absorption pathwayIron transport and storage machinerySystemic iron regulation

Iron supplementation (replenishing stores), Iron chelation (removing excess iron), Hepcidin agonism (inhibiting ferroportin to reduce iron levels), HIF2α inhibition (downregulating iron transporters), and Transferrin receptor targeting (for drug delivery or inhibiting uptake).