The TECPR1:ATG5-ATG12 complex conjugates LC3/ATG8 to damaged lysosomes that expose luminal glycans in response to osmotic imbalance
Hydrolytic enzymes within lysosomes maintain cell and tissue homoeostasis by degrading macromolecules delivered by endocytosis and autophagy. The release of lysosomal enzymes into the cytosol can induce apoptosis and “lysosome-dependent cell death” making it important for damaged lysosomes to be rep...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Autophagy Reports |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/27694127.2025.2476218 |
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| author | Yingxue Wang Matthew Jefferson Maria Ramos Matthew Whelband Kristin Kreuzer Grace Khuu Michael Lazarou James Mccoll James Lazenby Cynthia B Whitchurch Paul Verkade Ulrike Mayer Thomas Wileman |
| author_facet | Yingxue Wang Matthew Jefferson Maria Ramos Matthew Whelband Kristin Kreuzer Grace Khuu Michael Lazarou James Mccoll James Lazenby Cynthia B Whitchurch Paul Verkade Ulrike Mayer Thomas Wileman |
| author_sort | Yingxue Wang |
| collection | DOAJ |
| description | Hydrolytic enzymes within lysosomes maintain cell and tissue homoeostasis by degrading macromolecules delivered by endocytosis and autophagy. The release of lysosomal enzymes into the cytosol can induce apoptosis and “lysosome-dependent cell death” making it important for damaged lysosomes to be repaired or removed. Extensive lysosome damage exposes luminal sugars to galectin-dependent autophagy pathways that use ATG16L1:ATG5-ATG12 complex to conjugate LC3/ATG8 to autophagosomes to facilitate removal by lysophagy. Sphingomyelin exposed on stressed lysosomes recruits the lysosome tethering protein TECPR1 (tectonin beta propeller repeat-containing protein) allowing an alternative TECRP1:ATG5-ATG12 complex to conjugate LC3 directly to lysosomes. Here we have used cells lacking ATG16L1 to follow the recruitment of TECPR1, galectin-3 and LC3/ATG8 to lysosomes in response to osmotic imbalance induced by chloroquine. TECPR1 was recruited to swollen lysosomes that exposed sphingomyelin. LC3II was absent from swollen lysosomes but located to small puncta that contained the V-ATPase and LAMP1. The presence of galectin-3 and PI4P in the small LC3 puncta suggested that the TECPR1:ATG5-ATG12 complex conjugates LC3 to lysosome remnants that have ruptured in response to osmotic imbalance. |
| format | Article |
| id | doaj-art-7ef2cdbaf33a41d8a4986717473bfb3e |
| institution | OA Journals |
| issn | 2769-4127 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autophagy Reports |
| spelling | doaj-art-7ef2cdbaf33a41d8a4986717473bfb3e2025-08-20T02:17:09ZengTaylor & Francis GroupAutophagy Reports2769-41272025-12-014110.1080/27694127.2025.2476218The TECPR1:ATG5-ATG12 complex conjugates LC3/ATG8 to damaged lysosomes that expose luminal glycans in response to osmotic imbalanceYingxue Wang0Matthew Jefferson1Maria Ramos2Matthew Whelband3Kristin Kreuzer4Grace Khuu5Michael Lazarou6James Mccoll7James Lazenby8Cynthia B Whitchurch9Paul Verkade10Ulrike Mayer11Thomas Wileman12Norwich Medical School, University of East Anglia, Norwich, UKNorwich Medical School, University of East Anglia, Norwich, UKNorwich Medical School, University of East Anglia, Norwich, UKNorwich Medical School, University of East Anglia, Norwich, UKNorwich Medical School, University of East Anglia, Norwich, UKWalter and Eliza Hall Institute of Medical Research, Parkville, AustraliaWalter and Eliza Hall Institute of Medical Research, Parkville, AustraliaSchool of Biological Sciences, University of East Anglia, Norwich, UKQuadram Institute Bioscience, Norwich Research Park, Norwich, UKSchool of Biological Sciences, University of East Anglia, Norwich, UKSchool of Biochemistry, Faculty of Life Sciences, University of Bristol, Bristol, UKSchool of Biological Sciences, University of East Anglia, Norwich, UKNorwich Medical School, University of East Anglia, Norwich, UKHydrolytic enzymes within lysosomes maintain cell and tissue homoeostasis by degrading macromolecules delivered by endocytosis and autophagy. The release of lysosomal enzymes into the cytosol can induce apoptosis and “lysosome-dependent cell death” making it important for damaged lysosomes to be repaired or removed. Extensive lysosome damage exposes luminal sugars to galectin-dependent autophagy pathways that use ATG16L1:ATG5-ATG12 complex to conjugate LC3/ATG8 to autophagosomes to facilitate removal by lysophagy. Sphingomyelin exposed on stressed lysosomes recruits the lysosome tethering protein TECPR1 (tectonin beta propeller repeat-containing protein) allowing an alternative TECRP1:ATG5-ATG12 complex to conjugate LC3 directly to lysosomes. Here we have used cells lacking ATG16L1 to follow the recruitment of TECPR1, galectin-3 and LC3/ATG8 to lysosomes in response to osmotic imbalance induced by chloroquine. TECPR1 was recruited to swollen lysosomes that exposed sphingomyelin. LC3II was absent from swollen lysosomes but located to small puncta that contained the V-ATPase and LAMP1. The presence of galectin-3 and PI4P in the small LC3 puncta suggested that the TECPR1:ATG5-ATG12 complex conjugates LC3 to lysosome remnants that have ruptured in response to osmotic imbalance.https://www.tandfonline.com/doi/10.1080/27694127.2025.2476218sphingomyelinAutophagygalectin 3LC3/ATG8lysosome damagechloroquine |
| spellingShingle | Yingxue Wang Matthew Jefferson Maria Ramos Matthew Whelband Kristin Kreuzer Grace Khuu Michael Lazarou James Mccoll James Lazenby Cynthia B Whitchurch Paul Verkade Ulrike Mayer Thomas Wileman The TECPR1:ATG5-ATG12 complex conjugates LC3/ATG8 to damaged lysosomes that expose luminal glycans in response to osmotic imbalance Autophagy Reports sphingomyelin Autophagy galectin 3 LC3/ATG8 lysosome damage chloroquine |
| title | The TECPR1:ATG5-ATG12 complex conjugates LC3/ATG8 to damaged lysosomes that expose luminal glycans in response to osmotic imbalance |
| title_full | The TECPR1:ATG5-ATG12 complex conjugates LC3/ATG8 to damaged lysosomes that expose luminal glycans in response to osmotic imbalance |
| title_fullStr | The TECPR1:ATG5-ATG12 complex conjugates LC3/ATG8 to damaged lysosomes that expose luminal glycans in response to osmotic imbalance |
| title_full_unstemmed | The TECPR1:ATG5-ATG12 complex conjugates LC3/ATG8 to damaged lysosomes that expose luminal glycans in response to osmotic imbalance |
| title_short | The TECPR1:ATG5-ATG12 complex conjugates LC3/ATG8 to damaged lysosomes that expose luminal glycans in response to osmotic imbalance |
| title_sort | tecpr1 atg5 atg12 complex conjugates lc3 atg8 to damaged lysosomes that expose luminal glycans in response to osmotic imbalance |
| topic | sphingomyelin Autophagy galectin 3 LC3/ATG8 lysosome damage chloroquine |
| url | https://www.tandfonline.com/doi/10.1080/27694127.2025.2476218 |
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