The ATG conjugation systems are important for degradation of the inner autophagosomal membrane

Science. 2016 Nov 25;354(6315):1036-1041. doi: 10.1126/science.aaf6136. Epub 2016 Oct 20.

Abstract

In macroautophagy, cytoplasmic contents are sequestered into the double-membrane autophagosome, which fuses with the lysosome to become the autolysosome. It has been thought that the autophagy-related (ATG) conjugation systems are required for autophagosome formation. Here, we found that autophagosomal soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) syntaxin 17-positive autophagosome-like structures could be generated even in the absence of the ATG conjugation systems, although at a reduced rate. These syntaxin 17-positive structures could further fuse with lysosomes, but degradation of the inner autophagosomal membrane was significantly delayed. Accordingly, autophagic activity in ATG conjugation-deficient cells was strongly suppressed. We suggest that the ATG conjugation systems, which are likely required for the closure (i.e., fission) of the autophagosomal edge, are not absolutely essential for autolysosome formation but are important for efficient degradation of the inner autophagosomal membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagosomes / metabolism*
  • Autophagy*
  • Autophagy-Related Protein 12 / genetics
  • Autophagy-Related Protein 12 / metabolism*
  • Autophagy-Related Protein 8 Family / genetics
  • Autophagy-Related Protein 8 Family / metabolism*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Intracellular Membranes / metabolism*
  • Lysosomes / metabolism
  • Membrane Fusion
  • Phosphatidylethanolamines / metabolism
  • Qa-SNARE Proteins / metabolism*

Substances

  • Autophagy-Related Protein 12
  • Autophagy-Related Protein 8 Family
  • Phosphatidylethanolamines
  • Qa-SNARE Proteins
  • STX17 protein, human
  • phosphatidylethanolamine