Systemic physiological iron homeostasis

Systemic physiological iron homeostasis is the complex regulatory network responsible for maintaining stable iron levels in the body, essential for oxygen transport, DNA synthesis, and electron transfer (Hentze et al., 2010). The system lacks an active excretory pathway, meaning iron balance is primarily controlled at the level of intestinal absorption and recycling from senescent erythrocytes by macrophages (Camaschella, 2015). The central molecular regulator of this process is hepcidin, a liver-produced peptide hormone that controls the systemic availability of iron by binding to ferroportin, the sole cellular iron exporter (Ganz, 2013). Binding of hepcidin leads to the internalization and degradation of ferroportin, thereby sequestering iron within cells and lowering plasma iron concentrations (Nemeth et al., 2004). Dysregulation of this axis is central to various pathologies; for instance, hepcidin deficiency leads to hereditary hemochromatosis, while its overproduction during chronic inflammation causes anemia of chronic disease (Kroot et al., 2011). Therapeutic interventions targeting this system include hepcidin mimetics like rusfertide to prevent iron overload and hepcidin antagonists or ferroportin inhibitors like vamifeport to treat iron-restricted anemias (Ganz, 2013).

Other names

Iron metabolismSystemic iron regulationHepcidin-ferroportin axis

Regulation of systemic iron levels through the modulation of the hepcidin-ferroportin axis, which controls iron absorption from the diet and iron release from cellular stores.