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The Iron Responsive Element (IRE), the Iron Regulatory Protein (IRP), and Cytosolic Aconitase

Posttranscriptional Regulation of Mammalian Iron Metabolism

  • Chapter
Metal Ions in Gene Regulation

Part of the book series: Chapman & Hall Microbiology Series ((CHMBS))

Abstract

The fundamental role of iron in the maintenance of human health has been apparent for many years. The requirement for iron in growth and development of organisms from bacteria to humans arises because it is an essential component of proteins that perform redox and nonredox roles in a number of cellular functions. Given that iron is one of the most abundant, chemically versatile, and reactive elements in our environment, it is not surprising that nature has made extensive use of its properties. However, there are two significant problems regarding the use of iron in biological systems: its low solubility, particularly as Fe(III), and its toxicity when present in excess because of its ability to induce formation of damaging free radicals. Organisms have developed a variety of mechanisms to acquire and make use of iron for a large number of necessary functions while simultaneously reducing the incidence of inappropriate effects of this micronutrient on cell viability. Recent investigations of the regulation of iron homeostasis in mammals have identified two unique proteins: the iron regulatory proteins or IRPs,1 which act as central regulators of iron utilization. IRPs appear to represent the only members of the aconitase family of proteins that function in gene regulation (Frishman and Hentze 1996; Rouault et al. 1992). IRPs are cytosolic RNA binding proteins that modulate synthesis of proteins that function in the uptake, storage, and utilization of iron by binding to their mRNAs, thereby affecting their translation or stability. Posttranslational regulation of IRP function by iron and phosphorylation, with subsequent effects on iron metabolism, are topics of current inquiry to those interested in posttranscriptional gene regulation, iron-sulfur protein structure and function, and regulation of iron homeostasis.

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  1. Richard S. Eisenstein
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Eisenstein, R.S., Kennedy, M.C., Beinert, H. (1998). The Iron Responsive Element (IRE), the Iron Regulatory Protein (IRP), and Cytosolic Aconitase. In: Silver, S., Walden, W. (eds) Metal Ions in Gene Regulation. Chapman & Hall Microbiology Series. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5993-1_7

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