RUNDC1 inhibits autolysosome formation and survival of zebrafish via clasping ATG14-STX17-SNAP29 complex

作者全名："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, Marek; Ma, Cong; Chen, Xing-Zhen; Tang, Jingfeng; Zhou, Cefan"

作者地址："[Zhang, Rui; Yang, Yuyan; He, Chao; Zhang, Xin; Liu, Nan; Yang, Jiaren; Liu, Shicheng; Yuan, Jinglei; Li, Shi; Dong, Xueying; Bai, Hua; Hu, Mengyu; Liao, Zhiquan; Huang, Yuan; Lyu, Hao; Xiao, Shuai; Guo, Dong; Tang, Jingfeng; Zhou, Cefan] Hubei Univ Technol, Natl Ctr Cellular Regulat & Mol Pharmaceut 111, Key Lab Ind Fermentat, Minist Educ, Wuhan 430068, Peoples R China; [Torraca, Vincenzo] London Sch Hyg & Trop Med, Dept Infect Biol, London, England; [Torraca, Vincenzo] Univ Westminster, Sch Life Sci, London, England; [Wang, Shen; Ma, Cong] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Minist Educ, Key Lab Mol Biophys, Wuhan, Peoples R China; [Wang, Shen; Ma, Cong] Huazhong Univ Sci & Technol, Collaborat Innovat Ctr Brain Sci, Wuhan, Peoples R China; [Gou, Dongzhi] Chongqing Med Univ, Sch Publ Hlth, Chongqing, Peoples R China; [Xie, Yufei] Changsha Univ Sci & Technol, Sch Food Sci & Bioengn, Changsha, Peoples R China; [He, Junling] Army Med Univ, Daping Hosp, Army Med Ctr, Dept Nephrol, Chongqing, Peoples R China; [Ali, Declan William; Chen, Xing-Zhen] Univ Alberta, Dept Biochem, Edmonton, AB, Canada; [Michalak, Marek] Univ Alberta, Fac Med & Dent, Dept Physiol, Membrane Prot Dis Res Grp, Edmonton, AB, Canada"

通信作者："Tang, JF; Zhou, CF (通讯作者)，Hubei Univ Technol, Natl Ctr Cellular Regulat & Mol Pharmaceut 111, Key Lab Ind Fermentat, Minist Educ, Wuhan 430068, Peoples R China."

来源：CELL DEATH AND DIFFERENTIATION

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001060921500001

JCR分区：Q1

影响因子：13.7

年份：2023

卷号：30

期号：10

开始页：2231

结束页：2248

文献类型：Article

关键词：　

摘要："Autophagy serves as a pro-survival mechanism for a cell or a whole organism to cope with nutrient stress. Our understanding of the molecular regulation of this fusion event remains incomplete. Here, we identified RUNDC1 as a novel ATG14-interacting protein, which is highly conserved across vertebrates, including zebrafish and humans. By gain and loss of function studies, we demonstrate that RUNDC1 negatively modulates autophagy by blocking fusion between autophagosomes and lysosomes via inhibiting the assembly of the STX17-SNAP29-VAMP8 complex both in human cells and the zebrafish model. Moreover, RUNDC1 clasps the ATG14-STX17-SNAP29 complex via stimulating ATG14 homo-oligomerization to inhibit ATG14 dissociation. This also prevents VAMP8 from binding to STX17-SNAP29. We further identified that phosphorylation of RUNDC1 Ser(379 )is crucial to inhibit the assembly of the STX17-SNAP29-VAMP8 complex via promoting ATG14 homo-oligomerization. In line with our findings, RunDC1 is crucial for zebrafish in their response to nutrient-deficient conditions. Taken together, our findings demonstrate that RUNDC1 is a negative regulator of autophagy that restricts autophagosome fusion with lysosomes by clasping the ATG14-STX17-SNAP29 complex to hinder VAMP8 binding."

基金机构：We are grateful to Prof. Daniel Klionsky and Prof. Annemarie Meijer for sharing the GFP-Lc3 transgenic zebrafish line. We also thank the Hubei University of Technology for financial and equipment support for this research.; Hubei University of Technology

基金资助正文：We are grateful to Prof. Daniel Klionsky and Prof. Annemarie Meijer for sharing the GFP-Lc3 transgenic zebrafish line. We also thank the Hubei University of Technology for financial and equipment support for this research.