Cellular iron handling pathways

Cellular iron handling pathways encompass the coordinated molecular mechanisms responsible for the uptake, storage, utilization, and export of iron to maintain cellular homeostasis [1, 9]. Key components include Transferrin Receptor 1 (TfR1) for iron entry via endocytosis, Ferritin for intracellular storage, and Ferroportin (FPN) for iron export into the circulation [3, 4]. These pathways are tightly regulated by the Hepcidin-Ferroportin axis and the Iron Regulatory Protein (IRP)/Iron-Responsive Element (IRE) system, which sense intracellular iron levels and modulate the translation of key transporters and storage proteins [8, 11]. Dysregulation of these pathways is a hallmark of various diseases; for instance, cancer cells often upregulate iron uptake (e.g., TfR1) and downregulate export to support rapid proliferation, while iron overload or deficiency leads to conditions like hemochromatosis or anemia [1, 5]. Therapeutic strategies targeting these pathways include iron chelators to deplete the labile iron pool, hepcidin mimetics to restrict iron availability, and ferroptosis inducers to trigger iron-dependent cell death in tumors [2, 10]. Monitoring these pathways involves biomarkers such as serum ferritin, transferrin saturation, and hepcidin levels to assess systemic and cellular iron status [3, 14].

Other names

Cellular iron metabolismIron homeostasis pathwaysIntracellular iron traffickingIron metabolic pathways

Iron chelation, hepcidin-mediated degradation of ferroportin, inhibition of transferrin receptor-mediated endocytosis, and induction of ferroptosis.