2. Academic Validation
  3. The ubiquitin ligase RNF115 is required for the clearance of damaged lysosomes

The ubiquitin ligase RNF115 is required for the clearance of damaged lysosomes

  • FEBS Lett. 2026 Apr 24. doi: 10.1002/1873-3468.70346.
Sae Nakanaga 1,  Toshiki Takahashi 1,  Akiko Kuma 2,  Hiroyuki Kawahara 1
Affiliations

Affiliations

  • 1 Laboratory of Cell Biology and Biochemistry, Department of Biological Sciences, Tokyo Metropolitan University, Japan.
  • 2 Graduate School of Medicine, Division of Health Sciences, The University of Osaka, Japan.
PMID: 42032884 DOI: 10.1002/1873-3468.70346
Abstract

Lysosomes play a critical role in the quality control of cellular organelles. However, lysosomal membranes can be damaged under a variety of conditions, leading to the onset of various diseases. Damaged lysosomes are selectively cleared via a ubiquitin-dependent mechanism, but the molecular mechanisms underlying this process have not been adequately elucidated. In this study, we found that RNF115 is a lysosomal damage-responsive ubiquitin Ligase that undergoes massive translocation from the cytosol to the p62/SQSTM1-positive puncta around ruptured lysosomes. In accordance with the changes in its distribution, the depletion of RNF115 delayed the removal of Gal3 from damaged lysosomes during the restoration process following lysosomal damage. These observations suggest that RNF115 is responsible for the clearance of damaged lysosomes.

Keywords

BAG6; E3 ubiquitin ligase; RNF115; autophagy; lysophagy; lysosomal membrane damage; lysosome.

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