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https://doi.org/10.1038/s41467-019-10096-1
Title: | STX17 dynamically regulated by Fis1 induces mitophagy via hierarchical macroautophagic mechanism | Authors: | Xian, H. Yang, Q. Xiao, L. Shen, H.-M. Liou, Y.-C. |
Issue Date: | 2019 | Publisher: | Nature Publishing Group | Citation: | Xian, H., Yang, Q., Xiao, L., Shen, H.-M., Liou, Y.-C. (2019). STX17 dynamically regulated by Fis1 induces mitophagy via hierarchical macroautophagic mechanism. Nature Communications 10 (1) : 2059. ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-019-10096-1 | Rights: | Attribution 4.0 International | Abstract: | Mitophagy is the selective autophagic targeting and removal of dysfunctional mitochondria. While PINK1/Parkin-dependent mitophagy is well-characterized, PINK1/Parkin-independent route is poorly understood. Using structure illumination microscopy (SR-SIM), we demonstrate that the SNARE protein Syntaxin 17 (STX17) initiates mitophagy upon depletion of outer mitochondrial membrane protein Fis1. With proteomics analysis, we identify the STX17-Fis1 interaction, which controls the dynamic shuffling of STX17 between ER and mitochondria. Fis1 loss results in aberrant STX17 accumulation on mitochondria, which exposes the N terminus and promotes self-oligomerization to trigger mitophagy. Mitochondrial STX17 interacts with ATG14 and recruits core autophagy proteins to form mitophagosome, followed by Rab7-dependent mitophagosome-lysosome fusion. Furthermore, Fis1 loss impairs mitochondrial respiration and potentially sensitizes cells to mitochondrial clearance, which is mediated through canonical autophagy machinery, closely linking non-selective macroautophagy to mitochondrial turnover. Our findings uncover a PINK1/Parkin-independent mitophagic mechanism in which outer mitochondrial membrane protein Fis1 regulates mitochondrial quality control. © 2019, The Author(s). | Source Title: | Nature Communications | URI: | https://scholarbank.nus.edu.sg/handle/10635/210681 | ISSN: | 20411723 | DOI: | 10.1038/s41467-019-10096-1 | Rights: | Attribution 4.0 International |
Appears in Collections: | Elements Staff Publications |
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