SNARE Proteins Are Required for Macroautophagy

Cell. 2011 Jul 22;146(2):290-302. doi: 10.1016/j.cell.2011.06.022.

Abstract

Macroautophagy mediates the degradation of long-lived proteins and organelles via the de novo formation of double-membrane autophagosomes that sequester cytoplasm and deliver it to the vacuole/lysosome; however, relatively little is known about autophagosome biogenesis. Atg8, a phosphatidylethanolamine-conjugated protein, was previously proposed to function in autophagosome membrane expansion, based on the observation that it mediates liposome tethering and hemifusion in vitro. We show here that with physiological concentrations of phosphatidylethanolamine, Atg8 does not act as a fusogen. Rather, we provide evidence for the involvement of exocytic Q/t-SNAREs in autophagosome formation, acting in the recruitment of key autophagy components to the site of autophagosome formation, and in regulating the organization of Atg9 into tubulovesicular clusters. Additionally, we found that the endosomal Q/t-SNARE Tlg2 and the R/v-SNAREs Sec22 and Ykt6 interact with Sso1-Sec9, and are required for normal Atg9 transport. Thus, multiple SNARE-mediated fusion events are likely to be involved in autophagosome biogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy*
  • Autophagy-Related Protein 8 Family
  • Autophagy-Related Proteins
  • Liposomes / metabolism
  • Membrane Proteins / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Phagosomes / metabolism*
  • Phosphatidylethanolamines / metabolism
  • Qa-SNARE Proteins / metabolism
  • SNARE Proteins / metabolism*
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • ATG8 protein, S cerevisiae
  • ATG9 protein, S cerevisiae
  • Autophagy-Related Protein 8 Family
  • Autophagy-Related Proteins
  • Liposomes
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Phosphatidylethanolamines
  • Qa-SNARE Proteins
  • SNARE Proteins
  • SSO1 protein, S cerevisiae
  • SSO2 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • TLG2 protein, S cerevisiae
  • phosphatidylethanolamine