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Lysosome-associated CASM: from upstream triggers to downstream effector mechanisms
Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
2025 (engelsk)Inngår i: Frontiers in Cell and Developmental Biology, E-ISSN 2296-634X, Vol. 13, artikkel-id 1559125Artikkel, forskningsoversikt (Fagfellevurdert) Published
Abstract [en]

Lysosomes are dynamic organelles critical for cellular degradation and signaling, safeguarded by a limiting membrane that prevents leakage of harmful contents into the cytoplasm. Upon lysosomal damage, cells deploy defensive mechanisms, including a key process called CASM (conjugation of ATG8 to single membranes), which lipidates ATG8 proteins onto the limiting membrane to support protective pathways. CASM operates through two pathways: VAIL, induced by lysosomal pH changes via V-ATPase and ATG16L1, and STIL, triggered by sphingomyelin exposure and mediated by TECPR1. This review examines CASM’s role in lysosomal damage responses, exploring the mechanisms of damaging agents, distinctions between VAIL and STIL, and the downstream effects of decorating lysosomes with ATG8, including effector recruitment for membrane repair or removal.

sted, utgiver, år, opplag, sider
Frontiers Media S.A., 2025. Vol. 13, artikkel-id 1559125
Emneord [en]
Atg8, atg8ylation, autophagy, CASM, lysosome damage, STIL, VAIL
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Identifikatorer
URN: urn:nbn:se:umu:diva-237756DOI: 10.3389/fcell.2025.1559125PubMedID: 40213394Scopus ID: 2-s2.0-105002238919OAI: oai:DiVA.org:umu-237756DiVA, id: diva2:1953043
Forskningsfinansiär
The Research Council of Norway, 325305The Research Council of Norway, 262652Tilgjengelig fra: 2025-04-17 Laget: 2025-04-17 Sist oppdatert: 2025-04-17bibliografisk kontrollert

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