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The Structure and Function of Iron Regulatory Factor

  • Chapter
Progress in Iron Research

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 356))

Abstract

The discovery of iron regulatory factor (IRF), a soluble cytoplasmic protein also referred to as iron-responsive element-binding protein (IRE-BP) or ferritin repressor protein (FRP), has led to the characterization of a coordinate post-transcriptional regulation of key proteins in cellular iron metabolism. 1-3 The control integrates cellular iron absorption by receptor-mediated endocytosis of transferrin, iron storage in ferritin and specific pathways of iron utilization (Fig.l). Most remarkably, iron appears to regulate its own intra-cellular homeostasis through mechanisms that act as feedback loops: IRF is active as a mRNA-binding protein only after iron deprivation. Under these conditions, it associates with the iron responsive elements (IRE) in the 5’ or 3’ untranslated mRNA-regions and thereby inhibits ferritin synthesis as well as transferrin receptor (TfR) mRNA degradation (Fig.l). As a result ferritin is less expressed and iron storage diminished, while TfR expression and iron uptake is increased. Both effects tend to compensate for the unavailability of cellular iron. Once the free iron pool has increased to higher levels, IRF becomes inactivated and presumably dissociates from the IREs. This permits a shift in the regulatory balance and results in facilitated iron deposition and reduced iron uptake. IRF can therefore be considered as both a sensor and regulator of intra-cellular iron.

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Authors and Affiliations

  1. Swiss Institute for Experimental Cancer Research (ISREC), CH-1066, Epalinges, Switzerland

    Lukas C. Kühn, Harald Hirling, Beric Henderson, Alice Emery-Goodman, Barbara Neupert & Pierre Kaldy

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  1. Lukas C. Kühn
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  2. Harald Hirling
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  3. Beric Henderson
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  4. Alice Emery-Goodman
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  5. Barbara Neupert
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  6. Pierre Kaldy
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Editors and Affiliations

  1. Shaare Zedek Medical Center and Hebrew University of Jerusalem, Jerusalem, Israel

    Chaim Hershko

  2. The Hebrew University Hadassah Medical School, Jerusalem, Israel

    Abraham M. Konijn

  3. Albert Einstein College of Medicine, Bronx, New York, USA

    Philip Aisen

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© 1994 Springer Science+Business Media New York

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Kühn, L.C., Hirling, H., Henderson, B., Emery-Goodman, A., Neupert, B., Kaldy, P. (1994). The Structure and Function of Iron Regulatory Factor. In: Hershko, C., Konijn, A.M., Aisen, P. (eds) Progress in Iron Research. Advances in Experimental Medicine and Biology, vol 356. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2554-7_11

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  • DOI: https://doi.org/10.1007/978-1-4615-2554-7_11

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6090-2

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