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Inducin triggers LC3-lipidation and ESCRT-mediated lysosomal membrane repair
Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).ORCID iD: 0000-0001-7930-0134
Department of Chemical Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, Dortmund, Germany.
Department of Chemical Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, Dortmund, Germany.
Department of Chemical Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, Dortmund, Germany.
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2023 (English)In: ChemBioChem (Print), ISSN 1439-4227, E-ISSN 1439-7633, Vol. 24, no 24, article id e202300579Article in journal (Refereed) Published
Abstract [en]

Lipidation of the LC3 protein has frequently been employed as a marker of autophagy. However, LC3-lipidation is also triggered by stimuli not related to canonical autophagy. Therefore, characterization of the driving parameters for LC3 lipidation is crucial to understanding the biological roles of LC3. We identified a pseudo-natural product, termed Inducin, that increases LC3 lipidation independently of canonical autophagy, impairs lysosomal function and rapidly recruits Galectin 3 to lysosomes. Inducin treatment promotes Endosomal Sorting Complex Required for Transport (ESCRT)-dependent membrane repair and transcription factor EB (TFEB)-dependent lysosome biogenesis ultimately leading to cell death.

Place, publisher, year, edition, pages
Wiley-VCH Verlagsgesellschaft, 2023. Vol. 24, no 24, article id e202300579
Keywords [en]
biological activity, endolysosomal membrane damage, LC3 lipidation, lysosomal membrane permeabilization, small molecule
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-216651DOI: 10.1002/cbic.202300579ISI: 001097711600001PubMedID: 37869939Scopus ID: 2-s2.0-85175865186OAI: oai:DiVA.org:umu-216651DiVA, id: diva2:1815407
Funder
Max Planck SocietySwedish Research Council, 2018-04585Swedish Research Council, 2022-02932Knut and Alice Wallenberg FoundationGöran Gustafsson Foundation for Research in Natural Sciences and MedicineEU, FP7, Seventh Framework Programme, FP7/2007-2013German Research Foundation (DFG), EXC 2033–390677874– RESOLVAvailable from: 2023-11-28 Created: 2023-11-28 Last updated: 2024-01-15Bibliographically approved

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Corkery, DaleWu, Yao-Wen

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