Cited by 147Iron Metabolism and DisordersMitochondrial Function and PathologyNeurological diseases and metabolism

Iron regulatory proteins secure mitochondrial iron sufficiency and function

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Galy, Bruno, Ferring-Appel, Dunja, Sauer, Sven W., Kaden, Sylvia, Lyoumi, Saïd, Puy, Herve, Kölker, Stefan, Gröne, Hermann-Josef +1 more·2010·Cell Metabolism

Abstract

Mitochondria supply cells with ATP, heme, and iron sulfur clusters (ISC), and mitochondrial energy metabolism involves both heme- and ISC-dependent enzymes. Here, we show that mitochondrial iron supply and function require iron regulatory proteins (IRP), cytosolic RNA-binding proteins that control mRNA translation and stability. Mice lacking both IRP1 and IRP2 in their hepatocytes suffer from mitochondrial iron deficiency and dysfunction associated with alterations of the ISC and heme biosynthetic pathways, leading to liver failure and death. These results uncover a major role of the IRPs in cell biology: to ensure adequate iron supply to the mitochondrion for proper function of this critical organelle.

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Crossref · 10.1016/j.cmet.2010.06.007

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  • Mice lacking IRPs completely in hepatocytes or duodenal enterocytes die early after birth, showing IRPs are needed for organismal survival.

    “Earlier work investigating mice with complete IRP deficiency in hepatocytes or duodenal enterocytes, respectively, had shown early post-natal death in both cases, reflecting essential functions of the IRPs for organismal survival (Galy et al., 2008, 2010).”

    From Iron Regulatory Proteins Mediate Host Resistance to Salmonella Infection (2015) · cites this paper as Galy et al., 2010

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Authors
Galy, B., Ferring-Appel, D., Sauer, S. W., Kaden, S., Lyoumi, S., Puy, H., Kölker, S., Gröne, H.-J., & Hentze, M. W.
Affiliations
  • European Molecular Biology Laboratory (DE)
  • Heidelberg University (DE)
  • German Cancer Research Center (DE)
Corresponding author
Hentze, Matthias W.
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2010-08
Volume
12
Issue
2
Pages
194-201
ISSN
1550-4131 (ISSN-L)
OpenAlex
W1995039474
Cited by
147
References
39
Citations by year
2026: 5 · 2025: 16 · 2024: 7 · 2023: 7 · 2022: 11 · 2021: 9 · 2020: 12 · 2019: 10 · 2018: 9 · 2017: 7 · 2016: 8 · 2015: 8 · 2014: 12 · 2013: 5 · 2012: 10
FWCI
5.22
Type
journal article
Language
en
Open access
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
Keywords
iron regulatory proteins, iron regulatory protein 1, IRP2, iron deficiency, iron-sulfur clusters, heme biosynthesis, mitochondrial dysfunction, hepatocytes, liver failure, RNA-binding proteins
MeSH terms
Animals, Energy Metabolism, Heme, Iron, Mice, Transgenic, Mitochondria, Liver Failure, Iron-Regulatory Proteins, Iron Regulatory Protein 1, Iron Regulatory Protein 2, Mice

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