RUNDC1 negatively mediates the fusion of autophagosomes with lysosomes via regulating SNARE complex assembly.
Autophagy
; 20(2): 454-456, 2024 02.
Article
in En
| MEDLINE
| ID: mdl-37876308
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autophagy
/
Autophagosomes
Limits:
Animals
Language:
En
Journal:
Autophagy
Year:
2024
Type:
Article
Affiliation country:
China