bims-lypmec 2026-04-26 papers

FEBS Lett. 2026 Apr 24.

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

Sae Nakanaga, Toshiki Takahashi, Akiko Kuma, Hiroyuki Kawahara.

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

DOI: https://doi.org/10.1002/1873-3468.70346

Front Endocrinol (Lausanne). 2026 ;17 1794600

Lysosomal dysfunction in diabetes and diabetic complications.

Xin Chen, Lishan Huang, Zhiwen Xiao, Libin Liu.

Lysosomes, as organelles with degradative, secretory and signaling functions in eukaryotic cells, play a pivotal role in maintaining cellular energy homeostasis and biological recycling processes. In recent years, lysosomal dysfunction has garnered extensive attention from scholars for its implications in neurodegenerative and autoimmune diseases. however, its role in the occurrence and progression of diabetes mellitus and its complications remains to be further explored. Therefore, this article summarizes the research progress on lysosomal dysfunction in diabetes and its complications, hoping to highlight a promising therapeutic direction.

Keywords: autophagy; diabetes; diabetic complications; lysosomal; lysosomal dysfunction

DOI: https://doi.org/10.3389/fendo.2026.1794600

J Cell Biol. 2026 May 04. pii: e202604009. [Epub ahead of print]225(5):

A pressure relief valve for lysosomes.

Layla M Nassar, Shawn M Ferguson.

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.

DOI: https://doi.org/10.1083/jcb.202604009

Sci Signal. 2026 Apr 21. 19(934): eadu5769

mTORC1 and nuclear ERK spatially control translation in cardiomyocytes through 4EBP1 phosphorylation.

Keita Uchida, Emily A Scarborough, Elizabeth Pruzinsky, Kathlyene R Stone, Hali Hartman, Daniel P Kelly, Jonathan J Edwards, Izhak Kehat, Benjamin L Prosser.

Cardiomyocytes depend on local translation for growth and can undergo directed growth in length or width in response to different stimuli. Protein synthesis is augmented during concentric hypertrophy, which leads to thickening of the heart muscle by increasing cardiomyocyte width. Protein synthesis is controlled at the translation initiation step, when ribosome loading onto transcripts is regulated by the sequential phosphorylation of the eukaryotic initiation factor 4E-binding protein 1 (4EBP1). Here, we identified a mode of 4EBP1 phosphorylation that was associated with concentric hypertrophy in cultured cardiomyocytes and mouse hearts. Whereas canonical phosphorylation of 4EBP1 by mTORC1 regulates global protein synthesis rates, mTORC1- and nuclear ERK-dependent phosphorylation of 4EBP1 was specifically activated during concentric but not eccentric hypertrophy. Nuclear ERK-dependent phosphorylation of 4EBP1 at Ser64 was necessary and sufficient to relocalize translation initiation sites closer to the nuclei. ERK activation drove redistribution of ribosomes and nascent translation toward the center of the cardiomyocyte without altering global mRNA distribution, leading to spatially enriched deposition of new sarcomeric protein in the cardiomyocyte interior. Together, these findings demonstrate that global protein synthesis can be spatially regulated by the activation of different kinases in distinct subcellular compartments and identify a mechanism that drives concentric hypertrophy.

DOI: https://doi.org/10.1126/scisignal.adu5769