PUBLICATION
RUNDC1 negatively mediates the fusion of autophagosomes with lysosomes via regulating SNARE complex assembly
- Authors
- Zhang, R., Torraca, V., Lyu, H., Xiao, S., Guo, D., Zhou, C., Tang, J.
- ID
- ZDB-PUB-231025-59
- Date
- 2023
- Source
- Autophagy 20(2): 454-456 (Journal)
- Registered Authors
- Torraca, Vincenzo
- Keywords
- ATG14-STX17-SNAP29, RUNDC1, autophagosomes, autophagy, lysosomes, zebrafish
- MeSH Terms
-
- Animals
- Autophagosomes*/metabolism
- Autophagy*/physiology
- Lysosomes/metabolism
- Membrane Fusion/physiology
- SNARE Proteins/metabolism
- Transcription Factors/metabolism
- Zebrafish/metabolism
- PubMed
- 37876308 Full text @ Autophagy
Citation
Zhang, R., Torraca, V., Lyu, H., Xiao, S., Guo, D., Zhou, C., Tang, J. (2023) RUNDC1 negatively mediates the fusion of autophagosomes with lysosomes via regulating SNARE complex assembly. Autophagy. 20(2):454-456.
Abstract
Macroautophagy/autophagy is an essential pro-survival mechanism activated in response to nutrient deficiency. The proper fusion between autophagosomes and lysosomes is a critical step for autophagic degradation. We recently reported that RUNDC1 (RUN domain containing 1) inhibits autolysosome formation via clasping the ATG14-STX17-SNAP29 complex to hinder VAMP8 binding. We showed that RUNDC1 colocalizes with LC3 and associates with mature autophagosomes in cell lines and the zebrafish model. We utilized liposome fusion and in vitro autophagosome-lysosome fusion assays to demonstrate that RUNDC1 inhibits autolysosome formation. Moreover, we found that RUNDC1 clasps the ATG14-STX17-SNAP29 complex via stimulating ATG14 homo-oligomerization to inhibit ATG14 dissociation, which in turn prevents VAMP8 from binding to STX17-SNAP29. Our results demonstrate that RUNDC1 is a negative regulator of autophagy that restricts autophagosome fusion with lysosomes and is crucial for zebrafish survival in nutrient-deficient conditions. Here, we summarize our findings and discuss their implications for our understanding of autophagy regulation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping