Mechanisms and roles of membrane-anchored ATG8s
Autophagy-related protein 8 (ATG8) family proteins, including LC3 and GABARAP subfamilies, are pivotal in canonical autophagy, driving autophagosome formation, cargo selection, and lysosomal fusion. However, recent studies have identified non-canonical roles for lipidated ATG8 in processes such as L...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2025.1532050/full |
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| author | Soo-Kyeong Lee Sang-Won Park Deok-Jin Jang Jin-A. Lee |
| author_facet | Soo-Kyeong Lee Sang-Won Park Deok-Jin Jang Jin-A. Lee |
| author_sort | Soo-Kyeong Lee |
| collection | DOAJ |
| description | Autophagy-related protein 8 (ATG8) family proteins, including LC3 and GABARAP subfamilies, are pivotal in canonical autophagy, driving autophagosome formation, cargo selection, and lysosomal fusion. However, recent studies have identified non-canonical roles for lipidated ATG8 in processes such as LC3-associated phagocytosis (LAP), LC3-associated endocytosis (LANDO), and lipidated ATG8-mediated secretory autophagy. These pathways expand ATG8’s functional repertoire in immune regulation, membrane repair, and pathogen clearance, as ATG8 becomes conjugated to single-membrane structures (e.g., phagosomes and lysosomes). This review examines the molecular mechanisms of ATG8 lipidation, focusing on its selective conjugation to phosphatidylethanolamine (PE) in autophagy and phosphatidylserine (PS) in CASM. We highlight LIR-based probes and LC3/GABARAP-specific deconjugases as critical tools that allow precise tracking and manipulation of ATG8 in autophagic and non-autophagic contexts. These advancements hold therapeutic promise for treating autophagy-related diseases, including cancer and neurodegenerative disorders, by targeting ATG8-driven pathways that maintain cellular homeostasis. |
| format | Article |
| id | doaj-art-58b94be41b114e5b89fc35f554856350 |
| institution | Kabale University |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-58b94be41b114e5b89fc35f5548563502025-01-28T06:41:06ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-01-011310.3389/fcell.2025.15320501532050Mechanisms and roles of membrane-anchored ATG8sSoo-Kyeong Lee0Sang-Won Park1Deok-Jin Jang2Jin-A. Lee3Department of Biological Sciences and Biotechnology, College of Life Sciences and Nanotechnology, Hannam University, Daejeon, Republic of KoreaResearch Institute of Invertebrate Vector, Kyungpook National University, Sangju, Republic of KoreaDepartment of Ecological Science, College of Ecology and Environment, Kyungpook National University, Sangju, Republic of KoreaDepartment of Biological Sciences and Biotechnology, College of Life Sciences and Nanotechnology, Hannam University, Daejeon, Republic of KoreaAutophagy-related protein 8 (ATG8) family proteins, including LC3 and GABARAP subfamilies, are pivotal in canonical autophagy, driving autophagosome formation, cargo selection, and lysosomal fusion. However, recent studies have identified non-canonical roles for lipidated ATG8 in processes such as LC3-associated phagocytosis (LAP), LC3-associated endocytosis (LANDO), and lipidated ATG8-mediated secretory autophagy. These pathways expand ATG8’s functional repertoire in immune regulation, membrane repair, and pathogen clearance, as ATG8 becomes conjugated to single-membrane structures (e.g., phagosomes and lysosomes). This review examines the molecular mechanisms of ATG8 lipidation, focusing on its selective conjugation to phosphatidylethanolamine (PE) in autophagy and phosphatidylserine (PS) in CASM. We highlight LIR-based probes and LC3/GABARAP-specific deconjugases as critical tools that allow precise tracking and manipulation of ATG8 in autophagic and non-autophagic contexts. These advancements hold therapeutic promise for treating autophagy-related diseases, including cancer and neurodegenerative disorders, by targeting ATG8-driven pathways that maintain cellular homeostasis.https://www.frontiersin.org/articles/10.3389/fcell.2025.1532050/fullautophagyLC3/GABARAPLIR motifnon-canonical autophagyLandoLAP |
| spellingShingle | Soo-Kyeong Lee Sang-Won Park Deok-Jin Jang Jin-A. Lee Mechanisms and roles of membrane-anchored ATG8s Frontiers in Cell and Developmental Biology autophagy LC3/GABARAP LIR motif non-canonical autophagy Lando LAP |
| title | Mechanisms and roles of membrane-anchored ATG8s |
| title_full | Mechanisms and roles of membrane-anchored ATG8s |
| title_fullStr | Mechanisms and roles of membrane-anchored ATG8s |
| title_full_unstemmed | Mechanisms and roles of membrane-anchored ATG8s |
| title_short | Mechanisms and roles of membrane-anchored ATG8s |
| title_sort | mechanisms and roles of membrane anchored atg8s |
| topic | autophagy LC3/GABARAP LIR motif non-canonical autophagy Lando LAP |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1532050/full |
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