Systemic iron transport and storage pathways

Systemic iron transport and storage pathways represent the integrated physiological network responsible for maintaining iron balance, primarily regulated by the hepcidin-ferroportin axis (Ganz, 2013, PubMed). Iron is absorbed from the diet via enterocytes, transported through the circulation bound to transferrin, and stored intracellularly within ferritin complexes to prevent the generation of toxic reactive oxygen species (Camaschella, 2015, NEJM). The liver-derived hormone hepcidin acts as the master regulator by binding to and inducing the degradation of ferroportin, the only known cellular iron exporter, thereby controlling the entry of iron into the plasma (Donovan et al., 2005, Nature). Dysregulation of these pathways is central to various pathologies, including hereditary hemochromatosis, where hepcidin deficiency leads to systemic iron overload, and anemia of chronic disease, where inflammatory cytokines elevate hepcidin and sequester iron away from developing red blood cells. Pharmacological interventions include iron supplements for deficiency, chelating agents like deferoxamine for overload, and emerging therapies such as hepcidin mimetics (e.g., rusfertide) for iron-loading anemias (Kautz et al., 2014, Science Translational Medicine). Monitoring these pathways through biomarkers like serum ferritin and transferrin saturation is essential for managing iron-related disorders and avoiding the risks of iron-mediated tissue damage.

Other names

Iron homeostasisHepcidin-ferroportin axisIron metabolismSystemic iron regulation

Therapeutic agents modulate these pathways by providing elemental iron for erythropoiesis, chelating excess iron to prevent oxidative tissue damage, mimicking the hormone hepcidin to restrict iron export into plasma, or directly inhibiting the ferroportin transporter to sequester iron.