Volume 34, No 2, Feb 2024

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 34 Issue 2, February 2024: 151-168

ORIGINAL ARTICLES

The STX17-SNAP47-VAMP7/VAMP8 complex is the default SNARE complex mediating autophagosome–lysosome fusion

Fenglei Jian^1,† , Shen Wang^2,† , Rui Tian¹ , Yufen Wang¹ , Chuangpeng Li¹ , Yan Li³ , Shixuan Wang³ , Chao Fang¹ , Cong Ma^2,* , Yueguang Rong^1,4,*

¹School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonostic Infectious Disease, Huazhong University of Science and Technology, Wuhan, Hubei, China
²Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China
³Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
⁴Cell Architecture Research Center, Huazhong University of Science and Technology, Wuhan, Hubei, China
^†These authors contributed equally: Fenglei Jian, Shen Wang
Correspondence: Cong Ma(cong.ma@hust.edu.cn)Yueguang Rong(rongyueguang@hust.edu.cn)

Autophagosome–lysosome fusion mediated by SNARE complexes is an essential step in autophagy. Two SNAP29-containing SNARE complexes have been extensively studied in starvation-induced bulk autophagy, while the relevant SNARE complexes in other types of autophagy occurring under non-starvation conditions have been overlooked. Here, we found that autophagosome–lysosome fusion in selective autophagy under non-starvation conditions does not require SNAP29-containing SNARE complexes, but requires the STX17-SNAP47-VAMP7/VAMP8 SNARE complex. Further, the STX17-SNAP47-VAMP7/VAMP8 SNARE complex also functions in starvation-induced autophagy. SNAP47 is recruited to autophagosomes following concurrent detection of ATG8s and PI(4,5)P2 via its Pleckstrin homology domain. By contrast, SNAP29-containing SNAREs are excluded from selective autophagy due to inactivation by O-GlcNAcylation under non-starvation conditions. These findings depict a previously unknown, default SNARE complex responsible for autophagosome–lysosome fusion in both selective and bulk autophagy, which could guide research and therapeutic development in autophagy-related diseases.

https://doi.org/10.1038/s41422-023-00916-x

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