Unsaturated fatty acids induce non-canonical autophagy |
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Authors: | Federico Pietrocola José Manuel Bravo‐San Pedro Guillermo Mariño Valentina Cianfanelli Amena Ben‐Younès Rodrigo Troncoso Maria Markaki Valentina Sica Valentina Izzo Kariman Chaba Chantal Bauvy Nicolas Dupont Oliver Kepp Patrick Rockenfeller Heimo Wolinski Frank Madeo Sergio Lavandero Patrice Codogno Francis Harper Gérard Pierron Nektarios Tavernarakis Francesco Cecconi Maria Chiara Maiuri Guido Kroemer |
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Affiliation: | 1. Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France;2. Gustave Roussy Comprehensive Cancer Center, Villejuif, France;3. INSERM, U1138, Paris, France;4. Université Paris Sud/Paris 11, Le Kremlin Bicêtre, France;5. Department of Biology, University of Rome ‘Tor Vergata’, Rome, Italy;6. Unit of Cell Stress and Survival, Danish Cancer Society Research Center, Copenhagen, Denmark;7. Advanced Center for Chronic Disease (ACCDiS), Faculty of Chemical & Pharmaceutical Sciences/Faculty of Medicine, University of Chile, Santiago, Chile;8. Institute of Nutrition and Food Technology, University of Chile, Santiago, Chile;9. Faculty of Medicine, Institute of Nutrition and Food Technology, University of Chile, Santiago, Chile;10. Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology‐Hellas, Heraklion, Greece;11. Université Paris Descartes, Sorbonne Paris Cité, Paris, France;12. INSERM, U1151, Paris, France;13. Institut Necker Enfants‐Malades, Paris, France;14. Cell Biology & Metabolomics Platforms, Gustave Roussy Comprehensive Cancer Center, Villejuif, France;15. Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria;16. BioTechMed Graz, Graz, Austria;17. Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas, TX, USA;18. CNRS, UMR8122, Villejuif, France;19. Department of Basic Sciences, Faculty of Medicine, University of Crete, Heraklion, Greece;20. Laboratory of Molecular Neuroembryology, IRCCS Fondazione Santa Lucia, Rome, Italy |
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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. |
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Keywords: | ATG5 beclin 1 brefeldin A GFP-LC3 RFP-FYVE |
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