To escape or not to escape, that is the question

Liao and Bussi discuss work from Marco et al., which identifies an endocytic mechanism for internalization of therapeutic ASOs.

rupress.org

To escape or not to escape, that is the question

Liao and Bussi discuss work from Marco et al., which identifies an endocytic mechanism for internalization of therapeutic ASOs.

rupress.org

Roadmap for Condensates in Cell Biology

This Roadmap clarifies terminology, core physics, biological roles, and key theoretical, computational, and experimental challenges to guide a coordinated effort toward a predictive understanding and ...

journals.aps.org

Bacterial extracellular vesicles promote membrane repair and tolerance to polymyxin B

E. coli releases vesicles that repair membrane damage and promote survival under antibiotic stress.

science.org

𝙈𝙚𝙢𝙗𝙧𝙖𝙣𝙚𝙨 𝙖𝙣𝙙 𝙩𝙝𝙚𝙞𝙧 𝙡𝙞𝙥𝙞𝙙𝙨 𝙖𝙣𝙙 𝙥𝙧𝙤𝙩𝙚𝙞𝙣𝙨 𝙞𝙣 𝙤𝙧𝙜𝙖𝙣𝙚𝙡𝙡𝙚 𝙗𝙞𝙤𝙜𝙚𝙣𝙚𝙨𝙞𝙨 - Spetses, Greece - May 2026 | Utrecht University

Utrecht University

spetses2026.sites.uu.nl

Research Fellow (Cell Biology/Biophysics/Bioengineering/Biochemistry)

The Institute for Digital Molecular Analytics and Science (IDMxS), officially launched on 1 December 2022, is a Research Centre of Excellence (RCE) supported by a total investment of around S$160 mill...

ntu.wd3.myworkdayjobs.com

DNA nanodevices detect an acidic nanolayer on the lysosomal surface - Nature Cell Biology

Tan and colleagues develop DNA nanodevices to detect the pH of the lysosomal outer surface, observing an acidic layer generated by TMEM175 that regulates lysosome positioning in response to changes in...

nature.com

Cathepsin C–Catalyzed Ligation Generates Intralysosomal Amyloid Fibrils from Dipeptide Esters

Amyloid fibril-associated endolysosomal dysfunction is implicated in multiple neurodegenerative diseases. We report the rapid generation of intralysosomal amyloid fibrils by simply treating cells with certain dipeptide methyl esters. Cathepsin C mediates the ligation of dipeptides into oligopeptides that, sequence-dependently, self-assemble into amyloid fibrils. Progressive fibril growth, not fibril deposition, mediates lysosomal membrane permeabilization. Cryo-electron tomography studies reveal intralysosomal fibrils and broken lysosomal membranes upon dipeptide treatment. Certain oligopeptide fibril structures are competent to cross-seed the aggregation of neurodegeneration-associated Tau(P301S) at lysosomal sites. Similarly, the degree of lysosomal membrane permeabilization and ESCRT-repair response can be tuned with dipeptide sequence variation. The presented Cathepsin C-dependent amyloid fibril formation approach lends itself toward the development of novel tools to further probe lysosomal biology and pathobiology. ### Competing Interest Statement The authors have declared no competing interest. National Institute on Aging, https://ror.org/049v75w11, RF1AG073418 National Center for Advancing Translational Sciences, https://ror.org/04pw6fb54 Department of Education, USA, P031S240270 Freedom Together Foundation Chan Zuckerberg Initiative (United States), CZII-2023–327779 George E. Hewitt Foundation for Medical Research

biorxiv.org

Cathepsin-dependent amyloid formation drives mechanical rupture of lysosomal membranes

Lysosomal membrane integrity is essential for cellular homeostasis, and its failure drives lysosomal storage disorders (LSD) and neurodegeneration. The dipeptide L-leucyl-L-leucine methyl ester (LLOMe) is widely used to model lysosomal damage, yet its mechanism remains poorly understood. The prevailing view holds that LLOMe polymerizes into membrane-permeabilizing peptide chains within the lysosomal lumen. Using cryo-electron tomography in cultured cells and primary neurons, we visualized the structural basis of LLOMe-induced lysosomal damage. We reveal that LLOMe forms amyloid structures within lysosomes that directly interact with and rupture the limiting membrane through mechanical stress. In vitro reconstitution confirms this amyloid-mediated mechanism. These findings establish a structural paradigm for lysosomal membrane disruption and provide insights into how disease-relevant protein aggregates, implicated in neurodegeneration and LSD, may compromise lysosomal integrity. ### Competing Interest Statement J.W.H. is a co-founder of Caraway Therapeutics, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (Caraway) and is a scientific advisory board member for Lyterian Therapeutics. Aligning Science Across Parkinson's, https://ror.org/03zj4c476, ASAP-000350, ASAP-000282, ASAP-024268 Boehringer Ingelheim Fonds, https://ror.org/00dkye506 Deutsche Forschungsgemeinschaft, https://ror.org/018mejw64, GRK 2566/1 Pew Scholars Program NIH Common Fund, https://ror.org/001d55x84, RF1NS125674, R01NS110395 Fred and Joan Goldberg Post-doctoral Fellowship European Research Council, 101041982

biorxiv.org

The membrane transition strongly enhances biopolymer condensation through prewetting - Nature Chemical Biology

Biopolymers can couple to membrane lipids and condense to prewet membranes. Here a range of membrane perturbations in reconstituted systems and cells show that the prewetting is sensitive to membrane ...

nature.com

The ATG8 E3-like ligases sense lysosomal damage and initiate ESCRT-mediated membrane repair - The EMBO Journal

After damage from pathogenic, chemical or physical stress, endolysosomal membranes are repaired and resealed by the endosomal sorting complex required for transport (ESCRT) machinery, but how this mem...

link.springer.com

Sense, plug, and seal: proteins as both rapid responders and constitutive barriers supporting organelle compartmentalization | Molecular Biology of the Cell

Although organellar compartmentalization is primarily established by the delimiting phospholipid bilayer membranes, the contribution of proteins has been less appreciated. Recently, studies across man...

doi.org

GPNMB is a biomarker for lysosomal dysfunction and is secreted via LRRK2-modulated lysosomal exocytosis

The secretion mechanism of the Parkinson’s disease risk factor GPNMB highlights lysosomal dysfunction as a disease mechanism.

science.org

Phagocytosis: a process that shapes immune responses to engulfed meals - Nature Reviews Immunology

In this Review, Li and Underhill discuss recent advances in understanding the process of phagocytosis. The authors highlight how phagocytosis is integral for innate immune sensing and explain how the ...

nature.com

Lysosomes signal through the epigenome to regulate longevity across generations

The epigenome is sensitive to metabolic inputs and is crucial for aging. Lysosomes act as a signaling hub to sense metabolic cues and regulate longevity. We found that lysosomal metabolic pathways sig...

science.org

Bioimage Analysis Specialist | King's College London

kcl.ac.uk

CHIP protects lysosomes from CLN4 mutant-induced membrane damage - Nature Cell Biology

Lee et al. use an aggregation-prone CLN4 mutant that causes lysosomal damage in neurons and show that in non-neurons, the ubiquitin ligase CHIP prevents CLN4-dependent lysotoxicity via microautophagy.

nature.com

Membrane Dynamics, Repair and Disease | Keystone Symposia

Join us at the Keystone Symposia on Membrane Dynamics, Repair and Disease, February 2026, in Keystone, with field leaders!

keysym.us

Membrane Dynamics, Repair and Disease | Keystone Symposia

Join us at the Keystone Symposia on Membrane Dynamics, Repair and Disease, February 2026, in Keystone, with field leaders!

keysym.us

The biophysical requirements that govern the efficient endosomal escape of designed mini-proteins - Nature Chemistry

ZF5.3 is a mini-protein that escapes endosomes efficiently. Work to understand the underlying mechanism now reveals that ZF5.3 unfolds at pH values lower than 5.5 through protonation of Zn(II)-bound H...

nature.com