Novel inducers of BECN1-independent autophagy: Cis-unsaturated fatty acids

Mireia Niso-Santano, José Manuel Bravo San Pedro, Maria Chiara Maiuri, Nektarios Tavernarakis, Francesco Cecconi, Frank Madeo, Patrice Codogno, Lorenzo Galluzzi, Guido Kroemer

Research output: Contribution to journalArticle

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 b). 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 cisunsaturated 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 healthpromoting effects of cis-unsaturated fatty acids are linked to their unusual capacity to stimulate noncanonical, BECN1-independent autophagic responses.

Original languageEnglish
Pages (from-to)575-577
Number of pages3
JournalAutophagy
Volume11
Issue number3
DOIs
Publication statusPublished - Jan 1 2015

Keywords

  • Caenorhabditis elegans
  • Noncanonical autophagy
  • Oleate
  • Palmitate
  • Saccharomyces cerevisiae
  • Stearate

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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