Deacetylated SNAP47 recruits HOPS to facilitate autophagosome-lysosome fusion independent of STX17
Abstract Autophagy, a conserved catabolic process implicated in a diverse array of human diseases, requires efficient fusion between autophagosomes and lysosomes to function effectively. Recently, SNAP47 has been identified as a key component of the dual-purpose SNARE complex mediating autophagosome...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-55906-x |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841544546005024768 |
|---|---|
| author | Fenglei Jian Shen Wang Wenmin Tian Yang Chen Shixuan Wang Yan Li Cong Ma Yueguang Rong |
| author_facet | Fenglei Jian Shen Wang Wenmin Tian Yang Chen Shixuan Wang Yan Li Cong Ma Yueguang Rong |
| author_sort | Fenglei Jian |
| collection | DOAJ |
| description | Abstract Autophagy, a conserved catabolic process implicated in a diverse array of human diseases, requires efficient fusion between autophagosomes and lysosomes to function effectively. Recently, SNAP47 has been identified as a key component of the dual-purpose SNARE complex mediating autophagosome-lysosome fusion in both bulk and selective autophagy. However, the spatiotemporal regulatory mechanisms of this SNARE complex remain unknown. In this study, we found that SNAP47 undergoes acetylation followed by deacetylation during bulk autophagy and mitophagy. The acetylation status of SNAP47 is regulated by the acetyltransferase CBP and the deacetylase HDAC2. Notably, the spatiotemporal regulatory dynamics of SNAP47 acetylation differ between bulk autophagy and mitophagy due to distinct regulation on the activity of acetyltransferase and deacetylase. Acetylated SNAP47 inhibits autophagosome-lysosome fusion by indirectly impeding SNARE complex assembly. Mechanistically, deacetylated SNAP47 recruits HOPS components to autophagic vacuoles independently of STX17 and STX17-SNAP47 interaction, while acetylated SNAP47 inhibits this recruitment, consequently leading to the failure of SNARE complex assembly. Taken together, our study uncovers a SNAP47 acetylation-dependent regulatory mechanism governing autophagosome-lysosome fusion by modulating the recruitment of HOPS to autophagic vacuoles without involving STX17, SNAP47-STX17 interaction and ternary SNARE complex formation. |
| format | Article |
| id | doaj-art-cc9e916895ac484bac3fc4deafddf995 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-cc9e916895ac484bac3fc4deafddf9952025-01-12T12:29:51ZengNature PortfolioNature Communications2041-17232025-01-0116111510.1038/s41467-025-55906-xDeacetylated SNAP47 recruits HOPS to facilitate autophagosome-lysosome fusion independent of STX17Fenglei Jian0Shen Wang1Wenmin Tian2Yang Chen3Shixuan Wang4Yan Li5Cong Ma6Yueguang Rong7School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and TechnologyKey Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and TechnologyCenter for Precision Medicine Multi-Omics Research, Institute of Advanced Clinical Medicine, Peking UniversityCenter for Precision Medicine Multi-Omics Research, Institute of Advanced Clinical Medicine, Peking UniversityDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyKey Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and TechnologySchool of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and TechnologyAbstract Autophagy, a conserved catabolic process implicated in a diverse array of human diseases, requires efficient fusion between autophagosomes and lysosomes to function effectively. Recently, SNAP47 has been identified as a key component of the dual-purpose SNARE complex mediating autophagosome-lysosome fusion in both bulk and selective autophagy. However, the spatiotemporal regulatory mechanisms of this SNARE complex remain unknown. In this study, we found that SNAP47 undergoes acetylation followed by deacetylation during bulk autophagy and mitophagy. The acetylation status of SNAP47 is regulated by the acetyltransferase CBP and the deacetylase HDAC2. Notably, the spatiotemporal regulatory dynamics of SNAP47 acetylation differ between bulk autophagy and mitophagy due to distinct regulation on the activity of acetyltransferase and deacetylase. Acetylated SNAP47 inhibits autophagosome-lysosome fusion by indirectly impeding SNARE complex assembly. Mechanistically, deacetylated SNAP47 recruits HOPS components to autophagic vacuoles independently of STX17 and STX17-SNAP47 interaction, while acetylated SNAP47 inhibits this recruitment, consequently leading to the failure of SNARE complex assembly. Taken together, our study uncovers a SNAP47 acetylation-dependent regulatory mechanism governing autophagosome-lysosome fusion by modulating the recruitment of HOPS to autophagic vacuoles without involving STX17, SNAP47-STX17 interaction and ternary SNARE complex formation.https://doi.org/10.1038/s41467-025-55906-x |
| spellingShingle | Fenglei Jian Shen Wang Wenmin Tian Yang Chen Shixuan Wang Yan Li Cong Ma Yueguang Rong Deacetylated SNAP47 recruits HOPS to facilitate autophagosome-lysosome fusion independent of STX17 Nature Communications |
| title | Deacetylated SNAP47 recruits HOPS to facilitate autophagosome-lysosome fusion independent of STX17 |
| title_full | Deacetylated SNAP47 recruits HOPS to facilitate autophagosome-lysosome fusion independent of STX17 |
| title_fullStr | Deacetylated SNAP47 recruits HOPS to facilitate autophagosome-lysosome fusion independent of STX17 |
| title_full_unstemmed | Deacetylated SNAP47 recruits HOPS to facilitate autophagosome-lysosome fusion independent of STX17 |
| title_short | Deacetylated SNAP47 recruits HOPS to facilitate autophagosome-lysosome fusion independent of STX17 |
| title_sort | deacetylated snap47 recruits hops to facilitate autophagosome lysosome fusion independent of stx17 |
| url | https://doi.org/10.1038/s41467-025-55906-x |
| work_keys_str_mv | AT fengleijian deacetylatedsnap47recruitshopstofacilitateautophagosomelysosomefusionindependentofstx17 AT shenwang deacetylatedsnap47recruitshopstofacilitateautophagosomelysosomefusionindependentofstx17 AT wenmintian deacetylatedsnap47recruitshopstofacilitateautophagosomelysosomefusionindependentofstx17 AT yangchen deacetylatedsnap47recruitshopstofacilitateautophagosomelysosomefusionindependentofstx17 AT shixuanwang deacetylatedsnap47recruitshopstofacilitateautophagosomelysosomefusionindependentofstx17 AT yanli deacetylatedsnap47recruitshopstofacilitateautophagosomelysosomefusionindependentofstx17 AT congma deacetylatedsnap47recruitshopstofacilitateautophagosomelysosomefusionindependentofstx17 AT yueguangrong deacetylatedsnap47recruitshopstofacilitateautophagosomelysosomefusionindependentofstx17 |