Atg9 establishes Atg2-dependent contact sites between the endoplasmic reticulum and phagophores

J Cell Biol. 2018 Aug 6;217(8):2743-2763. doi: 10.1083/jcb.201710116. Epub 2018 May 30.


The autophagy-related (Atg) proteins play a key role in the formation of autophagosomes, the hallmark of autophagy. The function of the cluster composed by Atg2, Atg18, and transmembrane Atg9 is completely unknown despite their importance in autophagy. In this study, we provide insights into the molecular role of these proteins by identifying and characterizing Atg2 point mutants impaired in Atg9 binding. We show that Atg2 associates to autophagosomal membranes through lipid binding and independently from Atg9. Its interaction with Atg9, however, is key for Atg2 confinement to the growing phagophore extremities and subsequent association of Atg18. Assembly of the Atg9-Atg2-Atg18 complex is important to establish phagophore-endoplasmic reticulum (ER) contact sites. In turn, disruption of the Atg2-Atg9 interaction leads to an aberrant topological distribution of both Atg2 and ER contact sites on forming phagophores, which severely impairs autophagy. Altogether, our data shed light in the interrelationship between Atg9, Atg2, and Atg18 and highlight the possible functional relevance of the phagophore-ER contact sites in phagophore expansion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / physiology
  • Autophagy-Related Proteins / genetics
  • Autophagy-Related Proteins / metabolism
  • Autophagy-Related Proteins / physiology*
  • Endoplasmic Reticulum / metabolism*
  • Lipid Metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • Phosphatidylinositol Phosphates / metabolism
  • Phosphatidylinositol Phosphates / physiology
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / physiology*


  • ATG18 protein, S cerevisiae
  • ATG2 protein, S cerevisiae
  • ATG9 protein, S cerevisiae
  • Autophagy-Related Proteins
  • Membrane Proteins
  • Phosphatidylinositol Phosphates
  • Saccharomyces cerevisiae Proteins
  • phosphatidylinositol 3-phosphate