Radulovic et al. show that phosphatidylinositol 3-phosphate (PI3P), produced by the phosphatidylinositol 3-kinase PIK3C3, is formed on ER domains after lysosome damage. ER domain PI3P helps to recruit...

Lennartz et al. introduce a correlative light and electron microscopy workflow, Lipid-CLEM, combining near-native lipid probes and on-section labelling via click chemistry. Lipid-CLEM quantitatively a...

Post-transcriptional regulation of mRNA translation was explored using Ribo-STAMP and single-cell RNA sequencing to reveal cell-type-specific and isoform-specific translation patterns across hipp...

SAVEMONEY is a computational tool that guides users to mix plasmids prior to nanopore sequencing, reducing the effective cost of whole-plasmid sequencing to below that of Sanger sequencing.

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

CRISPR screens in iPSC-derived neurons reveal that the E3 ubiquitin ligase CRL5SOCS4 ubiquitinates tau, that CUL5 expression is correlated with resilience in human Alzheimer’s disease, and that electron transport chain dysfunction alters tau degradation by the proteasome.

Using chemical photoswitchable reagents to exert purely wavelength-dependent control over biological systems in deep tissue and in vivo requires a concentration-independent design paradigm. Here, such...

Scientific Reports - Compact Calm1 promoter enables AAV mediated neuron-targeted expression in human iPSC-derived brain organoids

The genetically-encoded fluorescent glutamate sensor, iGluSnFR3, characterised by a high dynamic range and rapid on-kinetics, is an attractive sensor for glutamate imaging in the central nervous syste...

The eukaryotic vault particle is a giant ribonucleoprotein complex that assembles into an iconic barrel-like cage. Its cellular function has remained elusive despite extensive characterization. Using ...

B-1 cells are innate-like lymphocytes that play a critical role in homeostasis by secreting natural antibodies, typically IgM, and immunosuppressive molecules such as IL-10. However, the regulation of...

Neurons are shown to use fatty acid β-oxidation as a fuel source for memory formation upon intensive learning in Drosophila, challenging the view that neurons are unable to use fatty acids for energy ...

De novo protein design has emerged as a powerful strategy with the promise to create new tools. The practical performance of designed fluorophore binders, however, has remained far from meeting fluore...

A cluster of Drosophila clock neurons remodel their axonal arbors daily. Using volumetric electron microscopy at different times of day, Ispizua, Rodriguez-Caron, and colleagues reveal ultrastructural...

Proximity labeling allows proteomic mapping of subcellular structures. Here, Sroka et al. develop in situ APEX activation (iAPEX) to overcome limitations of labeling specificity and H2O2 toxicity, app...

Small peptide tags (like ALFA) cause minimal disruption of proteins, but they typically lack fluorescence, which would enable knockin screening. Now, antigen-stabilizing fluorescent protein-fused nano...

Photobleaching of fluorescent proteins often limits the acquisition of high-quality images in microscopy. StayGold, a novel dimeric green fluorescent protein recently monomerised through sequence engi...

Eukaryotic cells synthesise thousands of lipid species, yet the principles that organise them across compartments remain unclear. Here we introduce PAP-SL, parallel (immuno)affinity purification coupl...

Labeling the plasma membrane for advanced imaging remains a significant challenge. For time-lapse live cell imaging, probe internalization and photobleaching are major limitations affecting most membr...

Self-complementing bipartite fluorescent proteins (FPs) are useful tools for the detection of protein–protein proximity and for localizing fluorophores to membrane–membrane contact sites. Here, we rep...

The enzyme ABHD18 is shown to have a key role in cardiolipin metabolism in mitochondria, offering a potential route for a small-molecule treatment of the rare genetic disease Barth syndrome.

Processing of raw ratiometric biosensor images (for example based on FRET) into fully corrected "ratio maps" or "activation maps" — images showing the localized activation of th...

DeepMVP is a deep learning framework for predicting PTM sites and variant-induced alterations across six modification types, including phosphorylation, acetylation, methylation, sumoylation, ubiquitin...

Scholarly publishing relies on peer review to identify the best science. Yet finding willing and qualified reviewers to evaluate manuscripts has become an increasingly challenging task, possibly even ...