• Medientyp: E-Artikel
  • Titel: Mammalian Tissue Oxygen Levels Modulate Iron-Regulatory Protein Activities in Vivo
  • Beteiligte: Meyron-Holtz, Esther G.; Ghosh, Manik C.; Rouault, Tracey A.
  • Erschienen: American Association for the Advancement of Science (AAAS), 2004
  • Erschienen in: Science
  • Sprache: Englisch
  • DOI: 10.1126/science.1103786
  • ISSN: 0036-8075; 1095-9203
  • Entstehung:
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  • Beschreibung: <jats:p> The iron-regulatory proteins (IRPs) posttranscriptionally regulate expression of transferrin receptor, ferritin, and other iron metabolism proteins. Although both IRPs can regulate expression of the same target genes, IRP2 <jats:sup>–/–</jats:sup> mice significantly misregulate iron metabolism and develop neurodegeneration, whereas IRP1 <jats:sup>–/–</jats:sup> mice are spared. We found that IRP2 <jats:sup>–/–</jats:sup> cells misregulated iron metabolism when cultured in 3 to 6% oxygen, which is comparable to physiological tissue concentrations, but not in 21% oxygen, a concentration that activated IRP1 and allowed it to substitute for IRP2. Thus, IRP2 dominates regulation of mammalian iron homeostasis because it alone registers iron concentrations and modulates its RNA-binding activity at physiological oxygen tensions. </jats:p>