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ToolsWang, Yingxue, Jefferson, Matthew, Ramos, Maria, Whelband, Matthew, Kreuzer, Kristin, Khuu, Grace, Lazarou, Michael, Mccoll, James, Lazenby, James, Whitchurch, Cynthia B., Verkade, Paul, Mayer, Ulrike and Wileman, Thomas (2025) The TECPR1:ATG5-ATG12 complex conjugates LC3/ATG8 to damaged lysosomes that expose luminal glycans in response to osmotic imbalance. Autophagy Reports, 4 (1). ISSN 2769-4127
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Abstract
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.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding information: The Norwich Medical School, University of East Anglia supported PhD studies by KK and MW and BBSRC doctoral training program for MR. The author(s) gratefully acknowledge the support of the Biotechnology and Biological Sciences Research Council (BBSRC); this research was funded by the BBSRC Institute Strategic Programme Microbes and Food Safety BB/X011011/1 and its partner project project(s). This work was supported by the National Health and Medical Research Council (NHMRC) (GNT1106471 to M.L.), the Australian Research Council (ARC) Discovery Project (DP200100347 to M.L.). We would like to acknowledge the support of the Quadram Institute Bioscience Advanced Microscopy Facility and the UEA Henry Wellcome BioImaging Facility for microscopy support. |
| Uncontrolled Keywords: | atg16l1,autophagy,chloroquine,galectin 3,atg8,lysosome damage,osmotic stress,sphingomyelin,tecpr1,pharmacology,neuroscience (miscellaneous),oncology(nursing),geriatrics and gerontology ,/dk/atira/pure/subjectarea/asjc/3000/3004 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School Faculty of Science Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 03 Nov 2025 17:30 |
| Last Modified: | 04 Nov 2025 01:01 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/100880 |
| DOI: | 10.1080/27694127.2025.2476218 |
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