title: Unsaturated fatty acids induce non-canonical autophagy.
abstract: To obtain mechanistic insights into the cross talk between lipolysis and autophagy, two key metabolic responses to starvation, we screened the autophagy-inducing potential of a panel of fatty acids in human cancer cells. Both saturated and unsaturated fatty acids such as palmitate and oleate, respectively, triggered autophagy, but the underlying molecular mechanisms differed. Oleate, but not palmitate, stimulated an autophagic response that required an intact Golgi apparatus. Conversely, autophagy triggered by palmitate, but not oleate, required AMPK, PKR and JNK1 and involved the activation of the BECN1/PIK3C3 lipid kinase complex. Accordingly, the downregulation of BECN1 and PIK3C3 abolished palmitate-induced, but not oleate-induced, autophagy in human cancer cells. Moreover, Becn1(+/-) mice as well as yeast cells and nematodes lacking the ortholog of human BECN1 mounted an autophagic response to oleate, but not palmitate. Thus, unsaturated fatty acids induce a non-canonical, phylogenetically conserved, autophagic response that in mammalian cells relies on the Golgi apparatus.
authors.affiliation: Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France Gustave Roussy Comprehensive Cancer Center, Villejuif, France INSERM, U1138, Paris, France.
authors.forename: Mireia
authors.initials: M
authors.lastname: Niso-Santano
authors.affiliation: Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France Gustave Roussy Comprehensive Cancer Center, Villejuif, France INSERM, U1138, Paris, France Government College University, Faisalabad, Pakistan.
authors.forename: Shoaib Ahmad
authors.initials: SA
authors.lastname: Malik
authors.affiliation: Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France Gustave Roussy Comprehensive Cancer Center, Villejuif, France INSERM, U1138, Paris, France Université Paris Sud/Paris 11, Le Kremlin Bicêtre, France.
authors.forename: Federico
authors.initials: F
authors.lastname: Pietrocola
authors.affiliation: Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France Gustave Roussy Comprehensive Cancer Center, Villejuif, France INSERM, U1138, Paris, France.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Bravo-San Pedro
authors.affiliation: Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France Gustave Roussy Comprehensive Cancer Center, Villejuif, France INSERM, U1138, Paris, France.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Mariño
authors.affiliation: Department of Biology, University of Rome 'Tor Vergata', Rome, Italy Unit of Cell Stress and Survival, Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Valentina
authors.initials: V
authors.lastname: Cianfanelli
authors.affiliation: Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France Gustave Roussy Comprehensive Cancer Center, Villejuif, France INSERM, U1138, Paris, France.
authors.forename: Amena
authors.initials: A
authors.lastname: Ben-Younès
authors.affiliation: Advanced Center for Chronic Disease (ACCDiS), Faculty of Chemical & Pharmaceutical Sciences/Faculty of Medicine, University of Chile, Santiago, Chile Institute of Nutrition and Food Technology, University of Chile, Santiago, Chile Faculty of Medicine, Institute of Nutrition and Food Technology, University of Chile, Santiago, Chile.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Troncoso
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Markaki
authors.affiliation: Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France Gustave Roussy Comprehensive Cancer Center, Villejuif, France INSERM, U1138, Paris, France Université Paris Sud/Paris 11, Le Kremlin Bicêtre, France.
authors.forename: Valentina
authors.initials: V
authors.lastname: Sica
authors.affiliation: Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France Gustave Roussy Comprehensive Cancer Center, Villejuif, France INSERM, U1138, Paris, France.
authors.forename: Valentina
authors.initials: V
authors.lastname: Izzo
authors.affiliation: Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Kariman
authors.initials: K
authors.lastname: Chaba
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France INSERM, U1151, Paris, France Institut Necker Enfants-Malades, Paris, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Bauvy
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France INSERM, U1151, Paris, France Institut Necker Enfants-Malades, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dupont
authors.affiliation: Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France INSERM, U1138, Paris, France Cell Biology & Metabolomics Platforms, Gustave Roussy Comprehensive Cancer Center, Villejuif, France.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kepp
authors.affiliation: Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria BioTechMed Graz, Graz, Austria.
authors.forename: Patrick
authors.initials: P
authors.lastname: Rockenfeller
authors.affiliation: Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria BioTechMed Graz, Graz, Austria.
authors.forename: Heimo
authors.initials: H
authors.lastname: Wolinski
authors.affiliation: Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria BioTechMed Graz, Graz, Austria.
authors.forename: Frank
authors.initials: F
authors.lastname: Madeo
authors.affiliation: Advanced Center for Chronic Disease (ACCDiS), Faculty of Chemical & Pharmaceutical Sciences/Faculty of Medicine, University of Chile, Santiago, Chile Institute of Nutrition and Food Technology, University of Chile, Santiago, Chile Faculty of Medicine, Institute of Nutrition and Food Technology, University of Chile, Santiago, Chile Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Sergio
authors.initials: S
authors.lastname: Lavandero
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France INSERM, U1151, Paris, France Institut Necker Enfants-Malades, Paris, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Codogno
authors.affiliation: Gustave Roussy Comprehensive Cancer Center, Villejuif, France CNRS, UMR8122, Villejuif, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Harper
authors.affiliation: Gustave Roussy Comprehensive Cancer Center, Villejuif, France CNRS, UMR8122, Villejuif, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Pierron
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Greece Department of Basic Sciences, Faculty of Medicine, University of Crete, Heraklion, Greece.
authors.forename: Nektarios
authors.identifier: http://orcid.org/0000-0002-5253-1466
authors.initials: N
authors.lastname: Tavernarakis
authors.affiliation: Department of Biology, University of Rome 'Tor Vergata', Rome, Italy Unit of Cell Stress and Survival, Danish Cancer Society Research Center, Copenhagen, Denmark Laboratory of Molecular Neuroembryology, IRCCS Fondazione Santa Lucia, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cecconi
authors.affiliation: Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France Gustave Roussy Comprehensive Cancer Center, Villejuif, France INSERM, U1138, Paris, France.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Maiuri
authors.affiliation: Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France Gustave Roussy Comprehensive Cancer Center, Villejuif, France INSERM, U1138, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Galluzzi
authors.affiliation: Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France INSERM, U1138, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Paris, France Cell Biology & Metabolomics Platforms, Gustave Roussy Comprehensive Cancer Center, Villejuif, France Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France kroemer@orange.fr.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D000071186:Beclin-1; D017173:Caenorhabditis elegans; D002478:Cells, Cultured; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019301:Oleic Acid / Q000494:pharmacology; D019308:Palmitic Acid / Q000494:pharmacology; D012441:Saccharomyces cerevisiae; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D005231:Fatty Acids, Unsaturated; D008565:Membrane Proteins; D019301:Oleic Acid; D019308:Palmitic Acid
keywords: ATG5; GFP‐LC3; RFP‐FYVE; beclin 1; brefeldin A