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: Mireia Niso-Santano, Shoaib Ahmad Malik, 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, Lorenzo Galluzzi, Guido Kroemer
• Journal: The EMBO journal (EMBO J) Vol. 34 Issue 8 Pg. 1025-41 (Apr 15 2015) ISSN: 1460-2075 [Electronic] England
• PMID: 25586377 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 The Authors.

Chemical References

• Apoptosis Regulatory Proteins
• BECN1 protein, human
• Beclin-1
• Fatty Acids, Unsaturated
• Membrane Proteins
• Oleic Acid
• Palmitic Acid

Topics

• Animals
• Apoptosis Regulatory Proteins (genetics)
• Autophagy (drug effects, genetics)
• Beclin-1
• Caenorhabditis elegans
• Cells, Cultured
• Fatty Acids, Unsaturated (pharmacology)
• Female
• HeLa Cells
• Humans
• Membrane Proteins (genetics)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Oleic Acid (pharmacology)
• Palmitic Acid (pharmacology)
• Saccharomyces cerevisiae
• Up-Regulation (drug effects)