ATG14 controls SNARE-mediated autophagosome fusion with a lysosome

Rong Liu, Xiaoyong Zhi, Qing Zhong

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Autophagosome fusion with a lysosome constitutes the last barrier for autophagic degradation. It is speculated that this fusion process is precisely and tightly regulated. Recent genetic evidence suggests that a set of SNARE proteins, including STX17, SNAP29, and VAMP8, are essential for the fusion between autophagosomes and lysosomes. However, it remains unclear whether these SNAREs are fusion competent and how their fusogenic activity is specifically regulated during autophagy. Using a combination of biochemical, cell biology, and genetic approaches, we demonstrated that fusogenic activity of the autophagic SNARE complex is temporally and spatially controlled by ATG14/ Barkor/Atg14L, an essential autophagyspecific regulator of the class III phosphatidylinositol 3-kinase complex (PtdIns3K). ATG14 directly binds to the STX17-SNAP29 binary complex on autophagosomes and promotes STX17- SNAP29-VAMP8-mediated autophagosome fusion with lysosomes. ATG14 homo-oligomerization is required for SNARE binding and fusion promotion, but is dispensable for PtdIns3K stimulation and autophagosome biogenesis. Consequently, ATG14 homo-oligomerization is required for autophagosome fusion with a lysosome, but is dispensable for autophagosome biogenesis. These data support a key role of ATG14 in controlling autophagosome fusion with a lysosome.

Original languageEnglish (US)
Pages (from-to)847-849
Number of pages3
JournalAutophagy
Volume11
Issue number5
DOIs
StatePublished - Jan 1 2015

Fingerprint

SNARE Proteins
Lysosomes
Class III Phosphatidylinositol 3-Kinases
Phosphatidylinositol 3-Kinase
Autophagosomes
Autophagy
Cell Biology

Keywords

  • ATG14
  • Autophagosome
  • Barkor
  • Homo-oligomerization
  • LYsosome
  • Membrane fusion
  • Membrane tethering
  • Snap29
  • SNARE
  • Syntaxin 17
  • Vamp8

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

ATG14 controls SNARE-mediated autophagosome fusion with a lysosome. / Liu, Rong; Zhi, Xiaoyong; Zhong, Qing.

In: Autophagy, Vol. 11, No. 5, 01.01.2015, p. 847-849.

Research output: Contribution to journalArticle

Liu, Rong ; Zhi, Xiaoyong ; Zhong, Qing. / ATG14 controls SNARE-mediated autophagosome fusion with a lysosome. In: Autophagy. 2015 ; Vol. 11, No. 5. pp. 847-849.
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