Iron handling pathways

Iron handling pathways encompass the complex network of proteins and regulatory mechanisms that maintain systemic and cellular iron homeostasis. This system involves the absorption of dietary iron in the duodenum, its transport via transferrin, storage in ferritin, and recycling by macrophages. The hepcidin-ferroportin axis serves as the master regulator, where the hormone hepcidin controls the export of iron into the plasma by binding to and inducing the degradation of the exporter ferroportin [1, 4, 14]. Dysregulation of these pathways is central to various pathologies, including iron-deficiency anemia, hereditary hemochromatosis, and anemia of chronic disease [4, 14]. In cancer, iron handling is often hijacked to support rapid proliferation, and targeting these pathways—either through iron depletion or the induction of iron-dependent cell death (ferroptosis)—represents a promising therapeutic strategy [2, 12, 17]. Additionally, iron accumulation in the brain is linked to neurodegenerative disorders, making iron modulation a key area of research for diseases like Alzheimer's and Parkinson's [8, 17].

Other names

Iron metabolismIron homeostasisHepcidin-ferroportin axisCellular iron regulation

Therapeutic modulation of iron handling pathways involves iron chelation to remove excess iron, hepcidin agonism or antagonism to regulate systemic iron levels, ferroportin inhibition to prevent iron export, iron supplementation to treat deficiency, and the induction of ferroptosis to kill cancer cells.