Reference - Detail
| RRC ID | 88163 |
|---|---|
| Author | Peng K, Zhao G, Zhao H, Noda NN, Zhang H. |
| Title | The autophagy protein ATG-9 regulates lysosome function and integrity. |
| Journal | J Cell Biol |
| Abstract |
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. |
| Volume | 224(6) |
| Published | 2025-6-2 |
| DOI | 10.1083/jcb.202411092 |
| PII | 277375 |
| PMID | 40202485 |
| PMC | PMC11980680 |
| MeSH | Animals Autophagosomes / metabolism Autophagy* Autophagy-Related Proteins* / genetics Autophagy-Related Proteins* / metabolism Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Lysosomes* / metabolism Mutation Phosphatidylethanolamines / metabolism |
| Altmetric score |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 84 |
| Altmetric score changes over past 6months | 7.3 |
| Resource | |
| C.elegans | tm3425 tm3525 tm2508 |