Cited by 195Iron Metabolism and DisordersTrace Elements in HealthNeurological diseases and metabolism

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Iron Regulatory Proteins Are Essential for Intestinal Function and Control Key Iron Absorption Molecules in the Duodenum

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Galy, Bruno, Ferring-Appel, Dunja, Kaden, Sylvia, Gröne, Hermann-Josef, Hentze, Matthias W.·2008·Cell Metabolism

DOI 10.1016/j.cmet.2007.10.006

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Abstract

Iron regulatory proteins (IRPs) orchestrate the posttranscriptional regulation of critical iron metabolism proteins at the cellular level. Redundancy between IRP1 and IRP2 associated with embryonic lethality of doubly IRP-deficient mice has precluded the study of IRP function in vivo. Here we use Cre/Lox technology to generate viable organisms lacking IRP expression in a single tissue, the intestine. Mice lacking intestinal IRP expression develop intestinal malabsorption and dehydration postnatally and die within 4 weeks of birth. We demonstrate that IRPs control the expression of divalent metal transporter 1 (DMT1) mRNA and protein, a limiting intestinal iron importer. IRPs are also shown to be critically important to secure physiological levels of the basolateral iron exporter ferroportin. IRPs are thus essential for intestinal function and organismal survival and coordinate the synthesis of key iron metabolism proteins in the duodenum.

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Self-citation

Authors: Galy, B., Ferring-Appel, D., Kaden, S., Gröne, H.-J., & Hentze, M. W.
Affiliations: European Molecular Biology Laboratory (DE)
German Cancer Research Center (DE)
Corresponding author: Hentze, Matthias W.
ORCID: Galy, Bruno
Hentze, Matthias W.
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2008-01
Volume: 7
Issue: 1
Pages: 79-85
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2007.10.006
OpenAlex: W2031180114
Cited by: 195
References: 32
Citations by year: 2026: 6 · 2025: 8 · 2024: 5 · 2023: 10 · 2022: 7 · 2021: 5 · 2020: 12 · 2019: 6 · 2018: 9 · 2017: 7 · 2016: 4 · 2015: 7 · 2014: 15 · 2013: 14 · 2012: 15
FWCI: 14.07
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2024 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
Keywords: iron regulatory proteins, iron regulatory protein 1, IRP2, intestinal iron absorption, duodenum, DMT1, ferroportin, post-transcriptional regulation, iron metabolism, malabsorption, tissue-specific knockout mice, Cre-loxP recombination
MeSH terms: Ferroportin, Solute Carrier Family 11, Member 2, Animals, Duodenum, Epithelial Cells, Intestinal Mucosa, Intestines, Iron, Mice, Transgenic, Immunoblotting, Polymerase Chain Reaction, Cation Transport Proteins, Iron-Regulatory Proteins, Iron Regulatory Protein 1, Iron Regulatory Protein 2, Microscopy, Electron, Transmission, Mice

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Iron Regulatory Proteins Are Essential for Intestinal Function and Control Key Iron Absorption Molecules in the Duodenum

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