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Glucose Starvation or Pyruvate Dehydrogenase Activation Induce a Broad, ERK5-Mediated, Metabolic Remodeling Leading to Fatty Acid Oxidation

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 o...

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Autores principales: Khan, Abrar Ul Haq, Salehi, Hamideh, Alexia, Catherine, Valdivielso, Jose M., Bozic, Milica, Lopez-Mejia, Isabel C., Fajas, Lluis, Gerbal-Chaloin, Sabine, Daujat-Chavanieu, Martine, Gitenay, Delphine, Villalba, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104157/
https://www.ncbi.nlm.nih.gov/pubmed/35563698
http://dx.doi.org/10.3390/cells11091392
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author Khan, Abrar Ul Haq
Salehi, Hamideh
Alexia, Catherine
Valdivielso, Jose M.
Bozic, Milica
Lopez-Mejia, Isabel C.
Fajas, Lluis
Gerbal-Chaloin, Sabine
Daujat-Chavanieu, Martine
Gitenay, Delphine
Villalba, Martin
author_facet Khan, Abrar Ul Haq
Salehi, Hamideh
Alexia, Catherine
Valdivielso, Jose M.
Bozic, Milica
Lopez-Mejia, Isabel C.
Fajas, Lluis
Gerbal-Chaloin, Sabine
Daujat-Chavanieu, Martine
Gitenay, Delphine
Villalba, Martin
author_sort Khan, Abrar Ul Haq
collection PubMed
description 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.
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spelling pubmed-91041572022-05-14 Glucose Starvation or Pyruvate Dehydrogenase Activation Induce a Broad, ERK5-Mediated, Metabolic Remodeling Leading to Fatty Acid Oxidation Khan, Abrar Ul Haq Salehi, Hamideh Alexia, Catherine Valdivielso, Jose M. Bozic, Milica Lopez-Mejia, Isabel C. Fajas, Lluis Gerbal-Chaloin, Sabine Daujat-Chavanieu, Martine Gitenay, Delphine Villalba, Martin Cells Article 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. MDPI 2022-04-20 /pmc/articles/PMC9104157/ /pubmed/35563698 http://dx.doi.org/10.3390/cells11091392 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Khan, Abrar Ul Haq
Salehi, Hamideh
Alexia, Catherine
Valdivielso, Jose M.
Bozic, Milica
Lopez-Mejia, Isabel C.
Fajas, Lluis
Gerbal-Chaloin, Sabine
Daujat-Chavanieu, Martine
Gitenay, Delphine
Villalba, Martin
Glucose Starvation or Pyruvate Dehydrogenase Activation Induce a Broad, ERK5-Mediated, Metabolic Remodeling Leading to Fatty Acid Oxidation
title Glucose Starvation or Pyruvate Dehydrogenase Activation Induce a Broad, ERK5-Mediated, Metabolic Remodeling Leading to Fatty Acid Oxidation
title_full Glucose Starvation or Pyruvate Dehydrogenase Activation Induce a Broad, ERK5-Mediated, Metabolic Remodeling Leading to Fatty Acid Oxidation
title_fullStr Glucose Starvation or Pyruvate Dehydrogenase Activation Induce a Broad, ERK5-Mediated, Metabolic Remodeling Leading to Fatty Acid Oxidation
title_full_unstemmed Glucose Starvation or Pyruvate Dehydrogenase Activation Induce a Broad, ERK5-Mediated, Metabolic Remodeling Leading to Fatty Acid Oxidation
title_short Glucose Starvation or Pyruvate Dehydrogenase Activation Induce a Broad, ERK5-Mediated, Metabolic Remodeling Leading to Fatty Acid Oxidation
title_sort glucose starvation or pyruvate dehydrogenase activation induce a broad, erk5-mediated, metabolic remodeling leading to fatty acid oxidation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104157/
https://www.ncbi.nlm.nih.gov/pubmed/35563698
http://dx.doi.org/10.3390/cells11091392
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