Autophagy regulates fatty acid availability for oxidative phosphorylation through mitochondria-endoplasmic reticulum contact sites.
Animals
Autophagy
/ genetics
Cell Line, Tumor
Cell Proliferation
/ genetics
Endoplasmic Reticulum
/ genetics
Flow Cytometry
Humans
Leukemia
/ genetics
Leukemia, Myeloid, Acute
/ metabolism
Lipid Metabolism
/ genetics
Lipogenesis
/ genetics
Mice
Mitochondria
/ genetics
Oxidation-Reduction
Oxidative Phosphorylation
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
13 08 2020
13 08 2020
Historique:
received:
13
06
2019
accepted:
22
07
2020
entrez:
15
8
2020
pubmed:
15
8
2020
medline:
9
9
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32792483
doi: 10.1038/s41467-020-17882-2
pii: 10.1038/s41467-020-17882-2
pmc: PMC7426880
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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