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Journal Articles Nature Communications Year : 2020

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

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Aurélie Batut
  • Function : Author
  • PersonId : 1088475
Nicolas Espagnolle
Jean-Christophe Pagès
  • Function : Author
Justine Bertrand-Michel

Abstract

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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Dates and versions

inserm-02962997 , version 1 (09-10-2020)

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Claudie Bosc, Nicolas Broin, Marjorie Fanjul, Estelle Saland, Thomas Farge, et al.. Autophagy regulates fatty acid availability for oxidative phosphorylation through mitochondria-endoplasmic reticulum contact sites. Nature Communications, 2020, 11 (1), pp.4056. ⟨10.1038/s41467-020-17882-2⟩. ⟨inserm-02962997⟩
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