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Autophagosomal YKT6 is required for fusion with lysosomes independently of syntaxin 17

Matsui, Takahide, Jiang, Peidu, Nakano, Saori, Sakamaki, Yuriko, Yamamoto, Hayashi, Mizushima, Noboru·2018·Journal of Cell Biology
DOI 10.1083/jcb.201712058PMC PMC6080929
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Abstract

Macroautophagy is an evolutionarily conserved catabolic mechanism that delivers intracellular constituents to lysosomes using autophagosomes. To achieve degradation, lysosomes must fuse with closed autophagosomes. We previously reported that the soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) protein syntaxin (STX) 17 translocates to autophagosomes to mediate fusion with lysosomes. In this study, we report an additional mechanism. We found that autophagosome–lysosome fusion is retained to some extent even in STX17 knockout (KO) HeLa cells. By screening other human SNAREs, we identified YKT6 as a novel autophagosomal SNARE protein. Depletion of YKT6 inhibited autophagosome–lysosome fusion partially in wild-type and completely in STX17 KO cells, suggesting that YKT6 and STX17 are independently required for fusion. YKT6 formed a SNARE complex with SNAP29 and lysosomal STX7, both of which are required for autophagosomal fusion. Recruitment of YKT6 to autophagosomes depends on its N-terminal longin domain but not on the C-terminal palmitoylation and farnesylation that are essential for its Golgi localization. These findings suggest that two independent SNARE complexes mediate autophagosome–lysosome fusion.

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  • In vitro reconstitutions of autophagosome-vacuole and autophagosome-lysosome fusion have partially overcome the problem of analyzing fusion in intact cells and made it possible to identify relevant proteins and their functions in this specific step of autophagy.

    “In vitro reconstitutions of autophagosome-vacuole and autophagosome-lysosome fusion have partially overcome this problem and made it possible to identify relevant proteins and their functions in this specific step of autophagy.”

    From Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1 (2021) · cites this paper as [508]

  • Both autophagosome-vacuole fusion in yeast and autophagosome-lysosome fusion in mammals have been recently reconstituted using partially purified fractions of autophagosomes, vacuoles/lysosomes and cytosol.

    “Both autophagosome-vacuole fusion in yeast and autophagosome-lysosome fusion in mammals has been recently reconstituted, using partially purified fractions of autophagosomes, vacuoles/lysosomes and cytosol [506-508].”

    From Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1 (2021) · cites this paper as [508]

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Metadata

Authors
Matsui, T., Jiang, P., Nakano, S., Sakamaki, Y., Yamamoto, H., & Mizushima, N.
Affiliations
  • Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, The University of Tokyo, Tokyo, Japan 1
  • Research Core, Tokyo Medical and Dental University, Tokyo, Japan 2
ORCID
Mizushima, Noboru
Venue
Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2018-05-22
Volume
217
Issue
8
Pages
2633-2645
ISSN
  • 0021-9525
  • 1540-8140
DOI
10.1083/jcb.201712058
PMC
PMC6080929
Cited by
257
References
4
Language
en
Licence
Funders
  • Japan Society for the Promotion of Science (25111005)
  • Japan Science and Technology Agency
  • Exploratory Research for Advanced Technology (JPMJER1702)

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