Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.
Iron is vital for all processes of life. It is the fourth most abundant element of the Earth's crust and a crucial component of countless biochemical pathways. It can readily accept or donate electrons during the interconversion of Fe3+ and Fe2+, and this property is fundamental to many of its biological roles. Iron is integral to the catalysis of the redox reactions of oxidative phosphorylation in the respiratory chain, and it provides a specific binding site for oxygen in the heme-binding moiety of hemoglobin, which allows oxygen transport in the blood.
In contrast to these beneficial features, unless appropriately chelated, iron can catalyze the formation of highly reactive toxic compounds, such as hydroxyl radicals, via the Fenton and Haber-Weiss disproportionating reactions and can thereby lead to the damage of DNA and proteins and, hence, cellular destruction. Iron in the body must therefore be very carefully regulated. Furthermore, most environmental iron is in the Fe3+ state, which is almost insoluble at neutral pH. To overcome the virtual insolubility and potential toxicity of iron, a myriad of specialized transport systems and associated proteins have evolved to mediate regulated acquisition, transport, and storage of iron in a nontoxic way. We are gradually beginning to understand how these proteins individually and in concert serve to maintain cellular homeostasis of this crucial yet potentially very harmful metal ion. Recent studies of these proteins and their functions are shedding new light on the mechanisms underlying a wide range of human diseases associated with iron deficiency, iron overload, and other imbalances of iron metabolism.
The cloning of the transferrin receptor in 19841was a major breakthrough. However, it proved frustratingly difficult to make subsequent progress in the elucidation of the molecular mechanisms of iron transport. An understanding of iron deficiency, iron overload, …