Iron

Iron is the fourth most abundant metal on Earth. Iron can easily change valence and form complexes with oxygen, and iron-mediated reactions support the respiration of nearly all aerobic organisms. Unless appropriately shielded, iron catalyzes the formation of radicals that can damage biological molecules, cells, tissues, and entire organisms. Because of the inherent danger of iron, specialized molecules for the acquisition, transport, and storage of iron have evolved. Delivery of iron to most cells occurs following the binding of transferrin to transferrin receptors on the cell membrane. The transferrin-transferrin receptor complexes are then internalized by endocytosis and iron is released from transferrin by a process involving endosomal acidification and reduction. Extra iron is stored in ferritin. Intake of iron by the body is transported from guts to enterocytes through the natural resistance-associated macrophage protein/divalent metal transporter 1 and subsequently from enterocytes to the circulation through hepcidin-ferroportin complexes. Organisms and cells possess a limited ability to excrete excess iron. Cells are also equipped with a regulatory system that controls iron levels in the labile pool. Levels of iron modulate the capacity of iron regulatory proteins to bind to the iron-responsive elements in the untranslated regions of several mRNAs encoding proteins involved in iron metabolism, thus, control iron homeostasis at the cellular and organismal levels. Despite these homeostatic mechanisms, organisms can face the threat of either iron deficiency or iron overload. Acute iron overload from overdose is potentially life-threatening. Chronic iron overload leads to slowly developing damage to organs such as the heart, liver, and brain. Occupational inhalation exposures to iron may give rise to siderosis. Our developing knowledge of iron metabolism increasingly emphasizes both vital and threatening nature of this most important and abundant metal.