Physiologic iron-dependent pathways and proteins

Physiologic iron-dependent pathways and proteins encompass the complex network of molecules responsible for maintaining iron homeostasis in the body (NIH, 2024). Iron is an essential cofactor for numerous biological processes, including oxygen transport via hemoglobin, DNA synthesis through ribonucleotide reductase, and cellular energy production in the mitochondrial electron transport chain (UniProt, 2024). The regulation of these pathways is primarily managed by the hepcidin-ferroportin axis, which controls iron absorption in the gut and its release from storage sites like macrophages and hepatocytes (PubMed, 2023). Dysregulation of these pathways can lead to pathological states such as iron-deficiency anemia or iron overload disorders like hereditary hemochromatosis (StatPearls, 2023). Furthermore, iron-dependent cell death, known as ferroptosis, has emerged as a critical pathway in cancer and neurodegeneration (Nature Reviews Drug Discovery, 2017). Therapeutically, these pathways are targeted by iron chelators to treat overload, iron supplements for deficiency, and novel agents like HIF-PH inhibitors and hepcidin mimetics to manage anemia of chronic disease (NIH, 2024). These interventions aim to restore the delicate balance of iron required for cellular function while preventing the oxidative damage associated with free iron (Frontiers in Physiology, 2022).

Other names

Iron metabolismIron homeostasisIron-dependent pathwaysIron-regulated proteinsIron-dependent proteome

Iron chelation, inhibition of hypoxia-inducible factor prolyl hydroxylase (HIF-PH), hepcidin receptor agonism, and inhibition of ferroportin-mediated iron export.