New insights regarding SNARE proteins in autophagosome-lysosome fusion

Autophagy. 2021 Oct;17(10):2680-2688. doi: 10.1080/15548627.2020.1823124. Epub 2020 Sep 24.

Abstract

Macroautophagy/autophagy refers to the engulfment of cellular contents selected for lysosomal degradation. The final step in autophagy is the fusion of autophagosome with the lysosome, which is mediated by SNARE proteins. Of the SNAREs, autophagosome-localized Q-SNAREs, such as STX17 and SNAP29, and lysosome-localized R-SNAREs, such as VAMP8 or VAMP7, have been reported to be involved. Recent studies also reveal participation of the R-SNARE, YKT6, in autophagosome-lysosome fusion. These SNAREs, with the help of other regulatory factors, act coordinately to spatiotemporally control the fusion process. Besides regulating autophagosome-lysosome fusion, some SNAREs, such as STX17, also function in other autophagic processes, including autophagosome formation and mitophagy. A better understanding of the functions of SNAREs will shed light on the molecular mechanisms of autophagosome-lysosome fusion as well as on the mechanisms by which autophagy is globally regulated.Abbreviations: ATG: autophagy related; DNM1L: dynamin 1 like; ER: endoplasmic reticulum; GABARAP: GABA type A receptor-associated protein; GABARAPL1: GABA type A receptor associated protein like 1; IRGM: immunity related GTPase M; LAMP2: lysosomal associated membrane protein 2; MAP1LC3B/LC3: microtubule associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; PIK3R4: phosphoinositide-3-kinase regulatory subunit 4; PLEKHM1: pleckstrin homology and RUN domain containing M1; PRKN: PRKN RBR E3 ubiquitin protein ligase; RAB2A: RAB2A, member RAS oncogene family; RAB33B: RAB33B, member RAS oncogene family; RAB7A: RAB7A, member RAS oncogene family; RB1CC1: RB1 inducible coiled-coil 1; RTN3: reticulon 3; RUBCNL: rubicon like autophagy enhancer; SNARE: soluble N-ethylmaleimide-sensitive factor attachment protein receptor; SNAP29: synaptosomal associated protein 29; STX17: syntaxin 17; ULK1: unc-51 like autophagy activating kinase 1; VAMP7: vesicle associated membrane protein 7; VAMP8: vesicle associated membrane protein 8; YKT6: YKT6 v-SNARE homolog.

Keywords: Autophagosome-lysosome fusion; SNARE; STX17; autophagy; mitophagy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Autophagosomes* / metabolism
  • Autophagy / physiology
  • Lysosomes / metabolism
  • Macroautophagy*
  • Membrane Fusion / physiology
  • Qa-SNARE Proteins / metabolism
  • R-SNARE Proteins / metabolism
  • SNARE Proteins / metabolism

Substances

  • Qa-SNARE Proteins
  • R-SNARE Proteins
  • SNARE Proteins

Grants and funding

This work was supported by the National Natural Science Foundation of China (NSFC) [91954124 and 31871353], the National Key Research and Development Program of China, Stem Cell and Translational Research [2016YFA0100501], and the China Postdoctoral Science Foundation [2020M672116].