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

Ruben Gomez-Sanchez, Jaqueline Rose, Rodrigo Guimaraes, Muriel Mari, Daniel Papinski, Ester Rieter, Willie J. Geerts, Ralph Hardenberg, Claudine Kraft, Christian Ungermann*, Fulvio Reggiori*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

153 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)2743-2763
Number of pages21
JournalThe Journal of Cell Biology
Issue number8
Publication statusPublished - 6-Aug-2018


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

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