Domenico Iuso, Isabel Garcia-Saez, Yohann Couté, Yoshiki Yamaryo-Botté, Elisabetta Boeri Erba, Annie Adrait, Nour Zeaiter, Malgorzata Tokarska-Schlattner, Zuzana Macek Jilkova, Fayçal Boussouar, Sophie Barral, Luca Signor, Karine Couturier, Azadeh Hajmirza, Florent Chuffart, Ekaterina Bourova-Flin, Anne-Laure Vitte, Lisa Bargier, Denis Puthier, Thomas Decaens, Sophie Rousseaux, Cyrille Botté, Uwe Schlattner, Carlo Petosa, Saadi Khochbin
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...
September 8, 2023: Science Advances