Download MendeleyNucleoside diphosphate kinases 1 and 2 regulate a protective liver response to a high-fat diet.
Iuso, D., Garcia-Saez, I., Coute, Y., Yamaryo-Botte, 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., Botte, C., Schlattner, U., Petosa, C., Khochbin, S.(2023) Sci Adv 9: eadh0140-eadh0140
- PubMed: 37672589
- DOI: https://doi.org/10.1126/sciadv.adh0140
- Primary Citation of Related Structures:
7ZL8, 7ZLW, 7ZTK - PubMed 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.
Organizational Affiliation:
Univ. Grenoble Alpes, CNRS UMR 5309, INSERM U1209, Institute for Advanced Biosciences, La Tronche 38706, France.
