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Cited by 14Cancer, Lipids, and MetabolismLiver Disease Diagnosis and TreatmentLipid metabolism and biosynthesis

The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.

Nucleoside diphosphate kinases 1 and 2 regulate a protective liver response to a high-fat diet

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Iuso, Domenico, Garcia-Saez, Isabel, Couté, Yohann, Yamaryo-Botté, Yoshiki, Boeri Erba, Elisabetta, Adrait, Annie, Zeaiter, Nour, Tokarska-Schlattner, Malgorzata, Jilkova, Zuzana Macek, Boussouar, Fayçal, Barral, Sophie, Signor, Luca, Couturier, Karine, Hajmirza, Azadeh, Chuffart, Florent, Bourova-Flin, Ekaterina, Vitte, Anne-Laure, Bargier, Lisa, Puthier, Denis, Decaens, Thomas, Rousseaux, Sophie, Botté, Cyrille, Schlattner, Uwe, Petosa, Carlo, Khochbin, Saadi·2023·Science Advances
DOI 10.1126/sciadv.adh0140PMC PMC10482350

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Abstract

The synthesis of fatty acids from acetyl–coenzyme A (AcCoA) is deregulated in diverse pathologies, including cancer. Here, we report that fatty acid accumulation is negatively regulated by nucleoside diphosphate kinases 1 and 2 (NME1/2), housekeeping enzymes involved in nucleotide homeostasis that were recently found to bind CoA. We show that NME1 additionally binds AcCoA and that ligand recognition involves a unique binding mode dependent on the CoA/AcCoA 3′ phosphate. We report that Nme2 knockout mice fed a high-fat diet (HFD) exhibit excessive triglyceride synthesis and liver steatosis. In liver cells, NME2 mediates a gene transcriptional response to HFD leading to the repression of fatty acid accumulation and activation of a protective gene expression program via targeted histone acetylation. Our findings implicate NME1/2 in the epigenetic regulation of a protective liver response to HFD and suggest a potential role in controlling AcCoA usage between the competing paths of histone acetylation and fatty acid synthesis.

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Metadata

Authors
Iuso, D., Garcia-Saez, I., Couté, Y., Yamaryo-Botté, Y., Boeri Erba, E., Adrait, A., Zeaiter, N., Tokarska-Schlattner, M., Jilkova, Z. M., Boussouar, F., Barral, S., Signor, L., Couturier, K., Hajmirza, A., Chuffart, F., Bourova-Flin, E., Vitte, A.-L., Bargier, L., Puthier, D., Decaens, T., Rousseaux, S., Botté, C., Schlattner, U., Petosa, C., & Khochbin, S.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Univ. Grenoble Alpes, CNRS UMR 5309, INSERM U1209, Institute for Advanced Biosciences, La Tronche 38706, France.
  • Univ. Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale (IBS), Grenoble 38000, France.
  • Inserm (FR)
  • Univ. Grenoble Alpes, INSERM, Laboratory of Fundamental and Applied Bioenergetics, Grenoble, France.
Corresponding author
  • Petosa, Carlo
  • Khochbin, Saadi
ORCID
Venue
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Published
2023-09-08
Volume
9
Issue
36
Pages
eadh0140-eadh0140
ISSN
2375-2548 (ISSN-L)
DOI
10.1126/sciadv.adh0140
PMC
PMC10482350
OpenAlex
W4386474249
Cited by
14
References
8
Citations by year
2026: 1 · 2025: 6 · 2024: 4 · 2023: 3
FWCI
1.78
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Science Advances (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
  • UniTERAMO Research Catalog (University of Teramo) (submittedVersion, cc-by)
Funders
  • Aix-Marseille Université (ANR-10-INBS-0009-10)
  • Université Grenoble Alpes (ANR‐17‐EURE‐0003, ISBG; UMS 3518 CNRS-CEA-UGA-EMBL, ANR-15-IDEX-02, ANR-10-INBS-05-02)
  • European Molecular Biology Laboratory
  • Infrastructures en Biologie Santé et Agronomie (ANR-10-INBS-0009, ANR-17-EURE-0003, ANR-10-INBS-05-02)
  • Alliance Française contre les Maladies Parasitaires (ANR-11-LABX0024)
  • Alliance Nationale pour les Sciences de la Vie et de la Santé
  • Agence Nationale de la Recherche (ANR-10-INBS-0008, ANR-10-INBS-08, ANR-17-EURE-0003, ANR-19-CE12-0014, ANR-10-INBS-05-02, IDEX-02, ANR-10- INBS-05, ANR-10-INBS-0009, ANR-21-CE44-0010, ANR-17-EURE-, ANR‐15‐IDEX‐02, ANR‐19, ANR-15-IDEX-02 SYMER, Proteomics French Infrastructure,ANR-10-INBS-08, ANR-15-IDEX-0002, ANR-11-LABX-0024, ANR-17, ANR-10, ANR-10-INBS-0005, 15-IDEX-02, ANR-10-LABX-0049)
  • European Synchrotron Radiation Facility (ID30A-1)
  • Institut National de la Santé et de la Recherche Médicale
  • Fondation pour la Recherche Médicale (ANR-17-EURE-0003, EQU202103012700, ANR-10-INBS-05-02, FRM EQU202103012700)
  • Centre National de la Recherche Scientifique (ANR-11-LABX-0024)
  • Institut Universitaire de France
  • French Infrastructure for Integrated Structural Biology (ANR-17-EURE-0003, ANR-10-INBS-05–02, UMS 3518, ANR-10-INBS-0.5)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
  • Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords
nm23, NME2, acetyl-CoA, fatty acid synthesis, high-fat diet, hepatic steatosis, triglyceride synthesis, histone acetylation, epigenetic regulation, gene transcription, nucleotide homeostasis
MeSH terms
Animals, Fatty Acids, Histones, Liver, Nucleoside-Diphosphate Kinase, Mice, Knockout, Epigenesis, Genetic, Mice, Diet, High-Fat

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