title: Novel inducers of BECN1-independent autophagy: cis-unsaturated fatty acids.
abstract: The induction of autophagy usually requires the activation of PIK3C3/VPS34 (phosphatidylinositol 3-kinase, catalytic subunit type 3) within a multiprotein complex that contains BECN1 (Beclin 1, autophagy related). PIK3C3 catalyzes the conversion of phosphatidylinositol into phosphatidylinositol 3-phosphate (PtdIns3P). PtdIns3P associates with growing phagophores, which recruit components of the autophagic machinery, including the lipidated form of MAP1LC3B/LC3 (microtubule-associated protein 1 light chain 3 β). Depletion of BECN1, PIK3C3 or some of their interactors suppresses the formation of MAP1LC3B(+) phagophores or autophagosomes elicited by most physiological stimuli, including saturated fatty acids. We observed that cis-unsaturated fatty acids stimulate the generation of cytosolic puncta containing lipidated MAP1LC3B as well as the autophagic turnover of long-lived proteins in the absence of PtdIns3P accumulation. In line with this notion, cis-unsaturated fatty acids require neither BECN1 nor PIK3C3 to stimulate the autophagic flux. Such a BECN1-independent autophagic response is phylogenetically conserved, manifesting in yeast, nematodes, mice and human cells. Importantly, MAP1LC3B(+) puncta elicited by cis-unsaturated fatty acids colocalize with Golgi apparatus markers. Moreover, the structural and functional collapse of the Golgi apparatus induced by brefeldin A inhibits cis-unsaturated fatty acid-triggered autophagy. It is tempting to speculate that the well-established health-promoting effects of cis-unsaturated fatty acids are linked to their unusual capacity to stimulate noncanonical, BECN1-independent autophagic responses.
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer ; Centre de Recherche des Cordeliers ; Paris , France.
authors.forename: Mireia
authors.initials: M
authors.lastname: Niso-Santano
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Bravo-San Pedro
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Maiuri
authors.forename: Nektarios
authors.initials: N
authors.lastname: Tavernarakis
authors.forename: Francesco
authors.initials: F
authors.lastname: Cecconi
authors.forename: Frank
authors.initials: F
authors.lastname: Madeo
authors.forename: Patrice
authors.initials: P
authors.lastname: Codogno
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Galluzzi
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1; D020126:Brefeldin A / Q000737:chemistry; D017173:Caenorhabditis elegans; D045744:Cell Line, Tumor; D058546:Class III Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry*; D005231:Fatty Acids, Unsaturated / Q000737:chemistry*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism; D019301:Oleic Acid / Q000737:chemistry; D019308:Palmitic Acid / Q000737:chemistry; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000737:chemistry; D012441:Saccharomyces cerevisiae
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D020126:Brefeldin A; D058546:Class III Phosphatidylinositol 3-Kinases; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D049452:Green Fluorescent Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; D019301:Oleic Acid; D019308:Palmitic Acid; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates; C491997:BECN1 protein, human; C502070:MAP1LC3B protein, human; C055525:phosphatidylinositol 3-phosphate
keywords: Caenorhabditis elegans; Saccharomyces cerevisiae; noncanonical autophagy; oleate; palmitate; stearate