Titre
Glucose Starvation or Pyruvate Dehydrogenase Activation Induce a Broad, ERK5-Mediated, Metabolic Remodeling Leading to Fatty Acid Oxidation.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Khan, AUH
Auteure/Auteur
Salehi, H.
Auteure/Auteur
Alexia, C.
Auteure/Auteur
Valdivielso, J.M.
Auteure/Auteur
Bozic, M.
Auteure/Auteur
Lopez-Mejia, I.C.
Auteure/Auteur
Fajas, L.
Auteure/Auteur
Gerbal-Chaloin, S.
Auteure/Auteur
Daujat-Chavanieu, M.
Auteure/Auteur
Gitenay, D.
Auteure/Auteur
Villalba, M.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
2073-4409
Statut éditorial
Publié
Date de publication
2022-04-20
Volume
11
Numéro
9
Première page
1392
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Résumé
Cells have metabolic flexibility that allows them to adapt to changes in substrate availability. Two highly relevant metabolites are glucose and fatty acids (FA), and hence, glycolysis and fatty acid oxidation (FAO) are key metabolic pathways leading to energy production. Both pathways affect each other, and in the absence of one substrate, metabolic flexibility allows cells to maintain sufficient energy production. Here, we show that glucose starvation or sustained pyruvate dehydrogenase (PDH) activation by dichloroacetate (DCA) induce large genetic remodeling to propel FAO. The extracellular signal-regulated kinase 5 (ERK5) is a key effector of this multistep metabolic remodeling. First, there is an increase in the lipid transport by expression of low-density lipoprotein receptor-related proteins (LRP), e.g., CD36, LRP1 and others. Second, an increase in the expression of members of the acyl-CoA synthetase long-chain (ACSL) family activates FA. Finally, the expression of the enzymes that catalyze the initial step in each cycle of FAO, i.e., the acyl-CoA dehydrogenases (ACADs), is induced. All of these pathways lead to enhanced cellular FAO. In summary, we show here that different families of enzymes, which are essential to perform FAO, are regulated by the signaling pathway, i.e., MEK5/ERK5, which transduces changes from the environment to genetic adaptations.
PID Serval
serval:BIB_0CB7B6A1E909
PMID
Open Access
Oui
Date de création
2022-05-23T12:13:48.680Z
Date de création dans IRIS
2025-05-20T20:03:38Z
Fichier(s)![Vignette d'image]()
En cours de chargement...
Nom
35563698_BIB_0CB7B6A1E909.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by/4.0
Taille
1.77 MB
Format
Adobe PDF
PID Serval
serval:BIB_0CB7B6A1E909.P001
URN
urn:nbn:ch:serval-BIB_0CB7B6A1E9093
Somme de contrôle
(MD5):8d3935547b0a611d417b4c21ca21fabf