Journal Article

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

Batut, Aurélie, Cellular and Molecular Physiopathology of Obesity and Diabetes [Nice] ; Centre méditerranéen de médecine moléculaire (C3M) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UniCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UniCA), MetaToul FluxoMet (TBI-MetaToul) ; MetaboHUB-MetaToul ; MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL) ; Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Nation

2020

Overview

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.

• Publisher: Nature Publishing Group,CCSD,Nature Publishing Group UK,Nature Portfolio
• Subject: 13/106 / 13/109 / 13/89 / 14/19 / 14/28 / 631/67/1990/283 / 631/80/39 / 64 / 64/60 / 82/29 / 82/80 / 96 / 96/31 / 96/95 / Accumulation / Acute myeloid leukemia / Animals / Autophagy / Autophagy - genetics / Autophagy - physiology / Availability / Cancer / Catabolism / Cell Line, Tumor / Cell proliferation / Cell Proliferation - genetics / Cell Proliferation - physiology / Endoplasmic reticulum / Endoplasmic Reticulum - genetics / Endoplasmic Reticulum - metabolism / Fatty acids / Flow Cytometry / Humanities and Social Sciences / Humans / Leukemia / Leukemia - genetics / Leukemia - metabolism / Leukemia, Myeloid, Acute - metabolism / Leukemia, Myeloid, Acute - pathology / Life Sciences / Lipid metabolism / Lipid Metabolism - genetics / Lipid Metabolism - physiology / Lipids / Lipogenesis - genetics / Lipogenesis - physiology / Metabolism / Mice / Mitochondria / Mitochondria - genetics / Mitochondria - metabolism / multidisciplinary / Myeloid leukemia / Oxidation / Oxidation-Reduction / Oxidative metabolism / Oxidative Phosphorylation / Phagocytosis / Phosphorylation / Science / Science (multidisciplinary) / Tumorigenesis / Tumors
• ISBN: 0005642475000