Blood Iron Homeostasis: Newly Discovered Proteins and Iron Imbalance

In biological systems, iron exerts 2 contrasting effects. The chemical reactivity of iron is essential for the biological activities of proteins such as hemoglobin, ribonucleotide reductase, the cytochromes, and aconitases. However, free iron in a cell has the propensity to generate free radicals which can damage cellular components containing proteins, lipids, and nucleic acids. To maintain the balance between iron as an essential nutrient and iron as a potential cytotoxin, a number of biological protective mechanisms have evolved. As shown in the thalassemias, iron imbalance can have devastating effects on human health. Recently, several new proteins have been described that play critical roles in iron regulation including the master regulator of iron metabolism (hepcidin). In this review, we discuss the new knowledge that has arisen from studies in yeast and in humans, and we show how these studies are shedding new light on some well-known human disorders.

Abbreviations: Aα, alpha-amyloid peptide, APP, amyloid β precursor protein, β2M, beta 2 microglobulin, BMP, bone morphogenetic protein, Cp, ceruloplasmin, cytb561, cytochrome b561, DCT1, divalent cation transporter, Dcytb, duodenal cytochrome b, DMT1, divalent metal transporter 1, FPN1, ferroportin-1, FRDA, Friedreich's ataxia, FXN, frataxin, GPI, glycosylphosphatidylinositol, HCP1, heme carrier protein 1, HFE, hemochromatosis protein, HH, hereditary hemochromatosis, HIF1α, hypoxia inducible factor-1 α, HJV, hemojuvelin, Hp, hephaestin, IMP, integrin-mobilferrin pathway, IRE, iron response element, IRP, iron response protein, Lf, lactoferrin, LIP, labile iron pool, mHJV, glycosylphosphatidylinositol-anchored hemojuvelin, MTf, melanotransferrin, PCFT, proton-coupled folate transporter, RBCs, red blood cells, ROS, reactive oxygen species, sHJV, soluble hemojuvelin, SLA, sex-linked anemia, sMTf, soluble melanotransferrin, Tf, transferrin, TfR, transferrin receptor, TM, transmembrane, UTR, untranslated region