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.
基金:
National Natural Science Foundation of China (National Science Foundation of China) [92254302, 91854116, 32170685, 31771529]; NSFC [5003510089, 2023BR028]; Fundamental Research Funds for the Central Universities
第一作者单位:[1]Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Basic Med, Wuhan, Hubei, Peoples R China[2]Huazhong Univ Sci & Technol, State Key Lab Diag & Treatment Severe Zoonost Infe, Wuhan, Hubei, Peoples R China
共同第一作者:
通讯作者:
通讯机构:[1]Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Basic Med, Wuhan, Hubei, Peoples R China[2]Huazhong Univ Sci & Technol, State Key Lab Diag & Treatment Severe Zoonost Infe, Wuhan, Hubei, Peoples R China[5]Huazhong Univ Sci & Technol, Cell Architecture Res Ctr, Wuhan, Hubei, Peoples R China
推荐引用方式(GB/T 7714):
Jian Fenglei,Wang Shen,Tian Rui,et al.The STX17-SNAP47-VAMP7/VAMP8 complex is the default SNARE complex mediating autophagosome-lysosome fusion[J].CELL RESEARCH.2024,34(2):151-168.doi:10.1038/s41422-023-00916-x.
APA:
Jian, Fenglei,Wang, Shen,Tian, Rui,Wang, Yufen,Li, Chuangpeng...&Rong, Yueguang.(2024).The STX17-SNAP47-VAMP7/VAMP8 complex is the default SNARE complex mediating autophagosome-lysosome fusion.CELL RESEARCH,34,(2)
MLA:
Jian, Fenglei,et al."The STX17-SNAP47-VAMP7/VAMP8 complex is the default SNARE complex mediating autophagosome-lysosome fusion".CELL RESEARCH 34..2(2024):151-168