Iron-binding and storage pathways

Iron-binding and storage pathways are critical systems that maintain cellular and systemic iron homeostasis, balancing the requirement for iron in processes like erythropoiesis and DNA synthesis against the risk of oxidative damage from free iron (StatPearls, NBK448065). The pathway involves the transport of iron by transferrin and its intracellular storage within the ferritin complex, which can sequester up to 4,500 iron atoms in a non-toxic form (UniProt, P02794). Systemic regulation is primarily achieved through the hormone hepcidin, which induces the degradation of the iron exporter ferroportin, thereby controlling iron entry into the blood from the diet and macrophages (NIH, 2023). Dysregulation of these pathways is central to the pathogenesis of iron-deficiency anemia and iron overload disorders such as hereditary hemochromatosis (PubMed, 30503141). Therapeutic strategies include the use of iron supplements to treat deficiency and iron chelators like deferoxamine to manage overload (PubChem, CID 2973). Emerging therapies also target the regulatory components of the pathway, such as hepcidin mimetics, to treat conditions of iron maldistribution (Journal of Hepatology, 2021). These pathways are also increasingly recognized for their role in ferroptosis, a form of regulated cell death relevant to cancer and neurodegeneration (Nature, 2020).

Other names

Iron metabolismIron homeostasisIron uptake and storage

Drugs targeting these pathways function by either supplementing iron levels to replenish stores, sequestering excess iron to prevent oxidative damage, or modulating regulatory proteins like hepcidin and ferroportin to control systemic iron flux.