RUNDC1 negatively mediates the fusion of autophagosome with lysosomes via regulating SNARE complex assembly
RUNDC1 negatively mediates the fusion of autophagosome with lysosomes via regulating SNARE complex assembly
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DOI：
10.1080/15548627.2023.2274210
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发表时间：
2023
期刊：
影响因子：
13.3
通讯作者：
Jingfeng Tang
中科院分区：
文献类型：
--
作者：
Rui Zhang;Vincenzo Torraca;Cefan Zhou;Jingfeng Tang
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.
