[Recent progress in iron metabolism and iron-related anemia].

Iron is an essential metal not only in oxygen delivery, but also in cell proliferation and drug metabolism, while it is a very toxic metal producing reactive oxygen species(ROS). In order to avoid the toxicity and shortage of iron, the level of iron is strictly regulated in the body and cells. The central player regulating the amount of iron in the body is hepcidin. Hepcidin inhibits the release of iron from enterocytes and macrophages by accelerating the degradation of ferroportin, which is an exporter of iron. The amount of cellular iron is regulated by the IRE (iron responsive element) and IRP (iron regulatory protein) system. IRP1 and 2, whose activities depend on the concentration of cellular iron, bind to IRE, and regulate the translation of iron-related genes, which have IRE in 5' or 3'-UTR to balance iron uptake and utilization. Iron is utilized for the generation of heme and the iron-sulfur (Fe-S) cluster in mitochondoria. Mutations of genes involved in heme biosynthesis, iron-sulfur (Fe-S) cluster biogenesis, or Fe-S cluster transport cause an accumulation of iron in mitochondoria, leading to the onset of inherited sideroblastic anemia. The most common inherited sideroblastic anemia is X-linked sideroblastic anemia (XLSA) caused by mutations of the erythroid-specific delta-aminolevulinate synthase gene (ALAS2), which is the first enzyme involved in heme biosynthesis in erythroid cells. However, there are still significant numbers of cases with genetically undefined, inherited sideroblastic anemia. Molecular analysis of these cases will contribute to the understanding of mitochondrial iron metabolism.