Novel inducers of BECN1-independent autophagy: Cis-unsaturated fatty acids Academic Article uri icon

Overview

MeSH Major

  • Apoptosis Regulatory Proteins
  • Class III Phosphatidylinositol 3-Kinases
  • Fatty Acids
  • Fatty Acids, Unsaturated
  • Membrane Proteins
  • Microtubule-Associated Proteins

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.

publication date

  • January 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4502685

Digital Object Identifier (DOI)

  • 10.1080/15548627.2015.1017222

PubMed ID

  • 25714112

Additional Document Info

start page

  • 575

end page

  • 7

volume

  • 11

number

  • 3