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REVIEW article
Front. Cell Dev. Biol.
Sec. Cell Death and Survival
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1559125
This article is part of the Research Topic Survival Strategies: Cellular Responses to Stress and Damage View all 7 articles
Lysosome-associated CASM: From Upstream Triggers to Downstream Effector Mechanisms
Provisionally accepted- 1 University of Oslo, Oslo, Norway
- 2 Oslo University Hospital, Oslo, Nordland, Norway
- 3 Umeå University, Umeå, Västerbotten, Sweden
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.
Keywords: CASM, vail, STIL, Autophagy, Lysosome damage, atg8ylation, Atg8
Received: 11 Jan 2025; Accepted: 12 Mar 2025.
Copyright: © 2025 Kaur, Carlsson and Lystad. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Alf Håkon Lystad, University of Oslo, Oslo, Norway
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