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bioRxiv · 10.1101/2025.09.04.674289

A role for CASM in the repair of damaged Golgi architecture

Oh, S.·Ullah, S.·Saha, B.·Mandell, M. A.
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Abstract

The term CASM describes a process in which MAP1LC3B/LC3B and other Atg8-family proteins are covalently ligated to lipids in damaged endomembranes. While CASM is commonly described as a cytoprotective response to multiple types of membrane damage, how CASM helps cells maintain homeostasis is still unclear. Here, we show that CASM maintains Golgi apparatus architecture following the loss of TRIM46, a ubiquitin ligase with roles in microtubule organization. TRIM46 deficient cells were notable for enhanced TFEB-driven lysosomal biogenesis and Golgi ribbon fragmentation, with colocalization of the trans-Golgi marker TGOLN2 and the Atg8-family proteins LC3B and GABARAP. Further studies revealed that the Golgi Atg8ylation seen in TRIM46 knockout cells was not degradative and mechanistically resembled CASM. Genetic inhibition of CASM in TRIM46 deficient cells reduced TFEB activation and exacerbated the Golgi morphology defects, suggesting that CASM contributes to Golgi repair. Accordingly, Golgi reformation after drug-induced fragmentation was impaired upon knockdown of CASM genes. Together, these studies identify lysosomal biogenesis and CASM as coordinated features of a Golgi damage response, with CASM acting to preserve Golgi integrity.

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Oh, S., Ullah, S., Saha, B., Mandell, M. A.. 2025-09-04. A role for CASM in the repair of damaged Golgi architecture. https://doi.org/10.1101/2025.09.04.674289

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