Iron, the Essential Micronutrient: A Comprehensive Review of Regulatory Pathways of Iron Metabolism

Iron constitutes an essential micronutrient in living organisms. All iron is absorbed into the body through dietary intake, except for exogenous therapeutic sources. Dietary iron is typically categorized as either heme or nonheme iron. Nonheme iron is essential for regulating iron in the body, as it exists in various forms, including soluble iron, storage iron within ferritin, and iron found in the catalytic centers of a wide range of proteins. Iron homeostasis is carefully managed to ensure that sufficient iron is available for critical biological processes while preventing the harmful effects that can arise from excess iron. The small peptide hormone hepcidin is the main regulator of iron homeostasis. Hepcidin and other iron regulatory molecules are regulated by various signaling pathways, such as IL-6/JAK-STAT, BMP/SMAD, and MAPK. Alterations in regulatory pathways may occur in response to iron accumulation or deficiency. Iron overload in the body can activate JAK/STAT, BMP/SMAD and MAPK pathways, leading to the initiation hepcidin synthesis. Conversely, in iron deficiency, as in hypoxic conditions or EPO-mediated signaling pathways, HAMP synthesis in the nucleus is reduced. Thus, this review provides an update on the possible regulatory pathways that play a role in iron regulation and may be potential therapeutic targets.