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Autophagy regulates fatty acid availability for oxidative phosphorylation through mitochondria-endoplasmic reticulum contact sites

Autophagy has been associated with oncogenesis with one of its emerging key functions being its contribution to the metabolism of tumors. Therefore, deciphering the mechanisms of how autophagy supports tumor cell metabolism is essential. Here, we demonstrate that the inhibition of autophagy induces...

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Autores principales: Bosc, Claudie, Broin, Nicolas, Fanjul, Marjorie, Saland, Estelle, Farge, Thomas, Courdy, Charly, Batut, Aurélie, Masoud, Rawand, Larrue, Clément, Skuli, Sarah, Espagnolle, Nicolas, Pagès, Jean-Christophe, Carrier, Alice, Bost, Frédéric, Bertrand-Michel, Justine, Tamburini, Jérôme, Récher, Christian, Bertoli, Sarah, Mansat-De Mas, Véronique, Manenti, Stéphane, Sarry, Jean-Emmanuel, Joffre, Carine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426880/
https://www.ncbi.nlm.nih.gov/pubmed/32792483
http://dx.doi.org/10.1038/s41467-020-17882-2
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author Bosc, Claudie
Broin, Nicolas
Fanjul, Marjorie
Saland, Estelle
Farge, Thomas
Courdy, Charly
Batut, Aurélie
Masoud, Rawand
Larrue, Clément
Skuli, Sarah
Espagnolle, Nicolas
Pagès, Jean-Christophe
Carrier, Alice
Bost, Frédéric
Bertrand-Michel, Justine
Tamburini, Jérôme
Récher, Christian
Bertoli, Sarah
Mansat-De Mas, Véronique
Manenti, Stéphane
Sarry, Jean-Emmanuel
Joffre, Carine
author_facet Bosc, Claudie
Broin, Nicolas
Fanjul, Marjorie
Saland, Estelle
Farge, Thomas
Courdy, Charly
Batut, Aurélie
Masoud, Rawand
Larrue, Clément
Skuli, Sarah
Espagnolle, Nicolas
Pagès, Jean-Christophe
Carrier, Alice
Bost, Frédéric
Bertrand-Michel, Justine
Tamburini, Jérôme
Récher, Christian
Bertoli, Sarah
Mansat-De Mas, Véronique
Manenti, Stéphane
Sarry, Jean-Emmanuel
Joffre, Carine
author_sort Bosc, Claudie
collection PubMed
description Autophagy has been associated with oncogenesis with one of its emerging key functions being its contribution to the metabolism of tumors. Therefore, deciphering the mechanisms of how autophagy supports tumor cell metabolism is essential. Here, we demonstrate that the inhibition of autophagy induces an accumulation of lipid droplets (LD) due to a decrease in fatty acid β-oxidation, that leads to a reduction of oxidative phosphorylation (OxPHOS) in acute myeloid leukemia (AML), but not in normal cells. Thus, the autophagic process participates in lipid catabolism that supports OxPHOS in AML cells. Interestingly, the inhibition of OxPHOS leads to LD accumulation with the concomitant inhibition of autophagy. Mechanistically, we show that the disruption of mitochondria–endoplasmic reticulum (ER) contact sites (MERCs) phenocopies OxPHOS inhibition. Altogether, our data establish that mitochondria, through the regulation of MERCs, controls autophagy that, in turn finely tunes lipid degradation to fuel OxPHOS supporting proliferation and growth in leukemia.
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spelling pubmed-74268802020-08-18 Autophagy regulates fatty acid availability for oxidative phosphorylation through mitochondria-endoplasmic reticulum contact sites Bosc, Claudie Broin, Nicolas Fanjul, Marjorie Saland, Estelle Farge, Thomas Courdy, Charly Batut, Aurélie Masoud, Rawand Larrue, Clément Skuli, Sarah Espagnolle, Nicolas Pagès, Jean-Christophe Carrier, Alice Bost, Frédéric Bertrand-Michel, Justine Tamburini, Jérôme Récher, Christian Bertoli, Sarah Mansat-De Mas, Véronique Manenti, Stéphane Sarry, Jean-Emmanuel Joffre, Carine Nat Commun Article Autophagy has been associated with oncogenesis with one of its emerging key functions being its contribution to the metabolism of tumors. Therefore, deciphering the mechanisms of how autophagy supports tumor cell metabolism is essential. Here, we demonstrate that the inhibition of autophagy induces an accumulation of lipid droplets (LD) due to a decrease in fatty acid β-oxidation, that leads to a reduction of oxidative phosphorylation (OxPHOS) in acute myeloid leukemia (AML), but not in normal cells. Thus, the autophagic process participates in lipid catabolism that supports OxPHOS in AML cells. Interestingly, the inhibition of OxPHOS leads to LD accumulation with the concomitant inhibition of autophagy. Mechanistically, we show that the disruption of mitochondria–endoplasmic reticulum (ER) contact sites (MERCs) phenocopies OxPHOS inhibition. Altogether, our data establish that mitochondria, through the regulation of MERCs, controls autophagy that, in turn finely tunes lipid degradation to fuel OxPHOS supporting proliferation and growth in leukemia. Nature Publishing Group UK 2020-08-13 /pmc/articles/PMC7426880/ /pubmed/32792483 http://dx.doi.org/10.1038/s41467-020-17882-2 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Bosc, Claudie
Broin, Nicolas
Fanjul, Marjorie
Saland, Estelle
Farge, Thomas
Courdy, Charly
Batut, Aurélie
Masoud, Rawand
Larrue, Clément
Skuli, Sarah
Espagnolle, Nicolas
Pagès, Jean-Christophe
Carrier, Alice
Bost, Frédéric
Bertrand-Michel, Justine
Tamburini, Jérôme
Récher, Christian
Bertoli, Sarah
Mansat-De Mas, Véronique
Manenti, Stéphane
Sarry, Jean-Emmanuel
Joffre, Carine
Autophagy regulates fatty acid availability for oxidative phosphorylation through mitochondria-endoplasmic reticulum contact sites
title Autophagy regulates fatty acid availability for oxidative phosphorylation through mitochondria-endoplasmic reticulum contact sites
title_full Autophagy regulates fatty acid availability for oxidative phosphorylation through mitochondria-endoplasmic reticulum contact sites
title_fullStr Autophagy regulates fatty acid availability for oxidative phosphorylation through mitochondria-endoplasmic reticulum contact sites
title_full_unstemmed Autophagy regulates fatty acid availability for oxidative phosphorylation through mitochondria-endoplasmic reticulum contact sites
title_short Autophagy regulates fatty acid availability for oxidative phosphorylation through mitochondria-endoplasmic reticulum contact sites
title_sort autophagy regulates fatty acid availability for oxidative phosphorylation through mitochondria-endoplasmic reticulum contact sites
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426880/
https://www.ncbi.nlm.nih.gov/pubmed/32792483
http://dx.doi.org/10.1038/s41467-020-17882-2
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