A pressure relief valve for lysosomes

2026/04/02 by Layla M. Nassar, Shawn M. Ferguson · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Calcium signaling and nucleotide metabolism #Cellular transport and secretion #Autophagy in Disease and Therapy

paper · doi:10.1083/jcb.202604009

Abstract

Several mechanisms repair damaged lysosomal membranes, but how can lysosomes prevent membrane failure in the first place? Kim et al. (https://doi.org/10.1083/jcb.202509180) uncover a rapid response whereby TMEM63A-dependent ion efflux relieves membrane tension, buying time for slower repair mechanisms to engage.

Citations

• Cathepsin-dependent amyloid formation drives mechanical rupture of lysosomal membranes
• TMEM63 proteins act as mechanically activated cholesterol modulated lipid scramblases contributing to membrane mechano-resilience

Discussions

• How do lysosomes rapidly adapt to membrane tension to avoid bursting? In this article, @laylanassar.bsky.social and I highlight discoveries from Angela Kim, Spencer Freeman and colleagues who show a [bsky, 22 points, 1 comments]

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