Nature Cell Biology - Wang et al. show the recruitment of the lipid channel protein VPS13C and formation of VPS13C-dependent contacts between endoplasmic reticulum and lysosomes after lysosomal...

Lysosome damage activates multiple pathways to prevent lysosome-dependent cell death, including a repair mechanism involving endoplasmic reticulum (ER…

Oligodendrocyte precursor cells (OPCs) play a multifaceted role in the brain. Here, the authors show that OPCs regulate neuronal metabolism by forming contacts with neuronal somata, facilitating lysos...

Lysosomes are essential in maintaining cellular health. Endocytic lysosome reformation (ELR) regenerates functional lysosomes following degradation of endocytic cargo, yet the mechanisms driving this process remain largely unknown. Here, we define the molecular machinery underlying ELR. We find that unlike autophagic lysosome reformation (ALR), ELR proceeds independently of mTOR and dynamin 2, but requires the mitochondrial fission GTPase DRP1. DRP1 mediates scission of endolysosomal tubules at contact sites with the endoplasmic reticulum (ER) and mitochondria. Disruption of DRP1 function or ER endolysosome contact results in elongated tubules, indicating defective lysosome reformation. Moreover, mitochondrial activity is essential for tubule initiation, and Ca2+ transfer from endolysosomes to mitochondria is crucial for ELR onset. Our findings reveal a dual role for mitochondria in ELR: first in ELR initiation and second in DRP1-dependent tubule fission at ER-mitochondria-endolysosome tripartite contact sites, uncovering the previously unappreciated role of mitochondria in endolysosome remodeling and fission. ### Competing Interest Statement The authors have declared no competing interest. Swiss National Science Foundation, 320030-231859, 310030-197779 University of Basel, https://ror.org/02s6k3f65

Lysosome damage activates multiple pathways to prevent lysosome-dependent cell death, including a repair mechanism involving endoplasmic reticulum (ER…

Effective lysosome function is essential for health, and declines with ageing and disease. Upon lysosome damage, cells mount a complex stress response to restore homeostasis. Membrane ATG8ylation play...

ATG8 conjugation on damaged lysosomes triggers rapid assembly of a protein complex containing TFG, which directs lysosomal membrane repair by recruiting ESCRT proteins to sites of damage.

Perturbations in lysosome integrity are tightly linked to neurological disorders and ageing, but the underlying pathogenic mechanisms are incompletely understood. Using an unbiased proteomic approach,...

There is growing evidence suggesting that the lysosome or lysosome dysfunction is associated with Alzheimers disease (AD). Pathway analysis of post mortem brain-derived proteomic data from AD patients...