2025-04-16 中国科学院(CAS)
Model for the involvement of ATG-9 in repair of damaged lysosomes (Image by ZHANG Hong’s group)
<関連情報>
- https://english.cas.cn/newsroom/research_news/life/202504/t20250414_1041202.shtml
- https://rupress.org/jcb/article-abstract/224/6/e202411092/277375/The-autophagy-protein-ATG-9-regulates-lysosome?redirectedFrom=fulltext
オートファジータンパク質ATG-9はリソソームの機能と完全性を制御する
The autophagy protein ATG-9 regulates lysosome function and integrity
Kangfu Peng,Guoxiu Zhao,Hongyu Zhao,Nobuo N. Noda,Hong Zhang
Journal Cell Biology Published:April 09 2025
DOI:https://doi.org/10.1083/jcb.202411092
The transmembrane autophagy protein ATG9 has multiple functions essential for autophagosome formation. Here, we uncovered a novel function of ATG-9 in regulating lysosome biogenesis and integrity in Caenorhabditis elegans. Through a genetic screen, we identified that mutations attenuating the lipid scrambling activity of ATG-9 suppress the autophagy defect in epg-5 mutants, in which non-degradative autolysosomes accumulate. The scramblase-attenuated ATG-9 mutants promote lysosome biogenesis and delivery of lysosome-localized hydrolases and also facilitate the maintenance of lysosome integrity. Through manipulation of phospholipid levels, we found that a reduction in phosphatidylethanolamine (PE) also suppresses the autophagy defects and lysosome damage associated with impaired lysosomal degradation. Our results reveal that modulation of phospholipid composition and distribution, e.g., by attenuating the scramblase activity of ATG-9 or reducing the PE level, regulates lysosome function and integrity.
