Lipid droplets are ubiquitous organelles in eukaryotes that act as storage sites for neutral lipids. Under normal growth conditions, they are not required in the yeast Saccharomyces cerevisiae. However, recent works have shown that lipid droplets are required for autophagy to proceed in response to nitrogen starvation and that they play an essential role in maintaining ER homeostasis. Autophagy is a major catabolic pathway that helps degradation and recycling of potentially harmful proteins and organelles. It can be pharmacologically induced by rapamycin even in the absence of lipid droplets. Here, we show that amino acid starvation is responsible for autophagy failure in lipid droplet-deficient yeast. It not only fails to induce autophagy but also inhibits rapamycin-induced autophagy. The general amino acid control pathway is not involved in this paradoxical effect of amino acid shortage. We correlate the autophagy failure with mitochondria aggregation and we show that amino acid starvation-induced autophagy is restored in lipid droplet-deficient yeast by increasing mitochondrial biomass physiologically (respiration) or genetically (REG1 deletion). Our results establish a new functional link between lipid droplets, ER and mitochondria during nitrogen starvation-induced autophagy.
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September 2020
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Cover Image
Cover Image
Thermogenesis of Arum maculatum. The cover of this issue of the Biochemical Journal features an image from Ito et al., who report the temperature-inducible degradation of AOX proteins in mitochondria from appendices of A. maculatum. Image courtesy of Kikukatsu Ito.
Research Article|
September 28 2020
Amino acid starvation inhibits autophagy in lipid droplet-deficient cells through mitochondrial dysfunction
Pierre Voisin;
Pierre Voisin
From Laboratoire Signalisation and Transports Ioniques Membranaires (STIM) EA7349, Université de Poitiers, Bâtiment B31, 3 rue Jacques Fort, TSA51106, 86073 Poitiers Cedex 9, France
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Marianne Bernard
;
Marianne Bernard
From Laboratoire Signalisation and Transports Ioniques Membranaires (STIM) EA7349, Université de Poitiers, Bâtiment B31, 3 rue Jacques Fort, TSA51106, 86073 Poitiers Cedex 9, France
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Thierry Bergès;
Thierry Bergès
From Laboratoire Signalisation and Transports Ioniques Membranaires (STIM) EA7349, Université de Poitiers, Bâtiment B31, 3 rue Jacques Fort, TSA51106, 86073 Poitiers Cedex 9, France
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Matthieu Régnacq
From Laboratoire Signalisation and Transports Ioniques Membranaires (STIM) EA7349, Université de Poitiers, Bâtiment B31, 3 rue Jacques Fort, TSA51106, 86073 Poitiers Cedex 9, France
Correspondence: Matthieu Régnacq (matthieu.regnacq@univ-poitiers.fr)
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Publisher: Portland Press Ltd
Received:
July 17 2020
Revision Received:
September 03 2020
Accepted:
September 04 2020
Accepted Manuscript online:
September 04 2020
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2020
Biochem J (2020) 477 (18): 3613–3623.
Article history
Received:
July 17 2020
Revision Received:
September 03 2020
Accepted:
September 04 2020
Accepted Manuscript online:
September 04 2020
Citation
Pierre Voisin, Marianne Bernard, Thierry Bergès, Matthieu Régnacq; Amino acid starvation inhibits autophagy in lipid droplet-deficient cells through mitochondrial dysfunction. Biochem J 30 September 2020; 477 (18): 3613–3623. doi: https://doi.org/10.1042/BCJ20200551
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