RUNDC1 negatively mediates the fusion of autophagosomes with lysosomes via regulating SNARE complex assembly

Zhang, Rui, Torraca, V., Lyu, Hao, Xiao, Shuai, Guo, Dong, Zhou, C. and Tang, J. 2024. RUNDC1 negatively mediates the fusion of autophagosomes with lysosomes via regulating SNARE complex assembly. Autophagy. 20 (2), pp. 454-456. https://doi.org/10.1080/15548627.2023.2274210

TitleRUNDC1 negatively mediates the fusion of autophagosomes with lysosomes via regulating SNARE complex assembly
TypeJournal article
AuthorsZhang, Rui, Torraca, V., Lyu, Hao, Xiao, Shuai, Guo, Dong, Zhou, C. and Tang, J.
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.

KeywordsCell Biology
Molecular Biology
JournalAutophagy
Journal citation20 (2), pp. 454-456
ISSN1554-8627
1554-8635
Year2024
PublisherTaylor & Francis
Digital Object Identifier (DOI)https://doi.org/10.1080/15548627.2023.2274210
Publication dates
Published online29 Oct 2023
Published in print2024
Project51808392
FunderNational Natural Science Foundation of China
University of Westminster

Related outputs

First person – Vincenzo Torraca
Torraca, V. 2024. First person – Vincenzo Torraca. Disease Models and Mechanisms. 17 (1) dmm050683. https://doi.org/10.1242/dmm.050683

Transcriptional profiling of zebrafish identifies host factors controlling susceptibility to Shigella flexneri
Torraca, V., White, R., Sealy, I., Mazon-Moya, M., Duggan, G., Willis, A., Busch-Nentwich, E. and Mostowy, S. 2024. Transcriptional profiling of zebrafish identifies host factors controlling susceptibility to Shigella flexneri. Disease Models and Mechanisms. 17 (1) dmm050431. https://doi.org/10.1242/dmm.050431

RUNDC1 inhibits autolysosome formation and survival of zebrafish via clasping ATG14-STX17-SNAP29 complex
Zhang, Rui, Yang, Yuyan, He, Chao, Zhang, Xin, Torraca, Vincenzo, Wang, Shen, Liu, Nan, Yang, Jiaren, Liu, Shicheng, Yuan, Jinglei, Gou, Dongzhi, Li, Shi, Dong, Xueying, Xie, Yufei, He, Junling, Bai, Hua, Hu, Mengyu, Liao, Zhiquan, Huang, Yuan, Lyu, Hao, Xiao, Shuai, Guo, Dong, Ali, Declan William, Michalak, M., Ma, C., Chen, X., Tang, J. and Zhou, C. 2023. RUNDC1 inhibits autolysosome formation and survival of zebrafish via clasping ATG14-STX17-SNAP29 complex. Cell Death and Differentiation. 30, p. 2231–2248. https://doi.org/10.1038/s41418-023-01215-z

Permalink - https://westminsterresearch.westminster.ac.uk/item/w80v0/rundc1-negatively-mediates-the-fusion-of-autophagosomes-with-lysosomes-via-regulating-snare-complex-assembly


Share this

Usage statistics

24 total views
0 total downloads
These values cover views and downloads from WestminsterResearch and are for the period from September 2nd 2018, when this repository was created.