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Cells sense physical forces and convert them into electrical or chemical signals, a process known as mechanotransduction. Whereas extensive studies focus on mechanotransduction at the plasma membrane, little is known about whether and how intracellular organelles sense mechanical force and the physiological functions of organellar mechanosensing. Here we identify the Drosophila TMEM63 (DmTMEM63) ion channel as an intrinsic mechanosensor of the lysosome, a major degradative organelle. Endogenous DmTMEM63 proteins localize to lysosomes, mediate lysosomal mechanosensitivity and modulate lysosomal morphology and function. Tmem63 mutant flies exhibit impaired lysosomal degradation, synaptic loss, progressive motor deficits and early death, with some of these mutant phenotypes recapitulating symptoms of TMEM63-associated human diseases. Importantly, mouse TMEM63A mediates lysosomal mechanosensitivity in Neuro-2a cells, indicative of functional conservation in mammals. Our findings reveal DmTMEM63 channel function in lysosomes and its physiological roles in vivo and provide a molecular basis to explore the mechanosensitive process in subcellular organelles.

For more than 100 years, the fruit fly Drosophila melanogaster has been one of the most studied model organisms. Here, we present a single-cell atlas of the adult fly, Tabula Drosophilae, that includes 580,000 nuclei from 15 individually dissected sexed tissues as well as the entire head and body, annotated to >250 distinct cell types. We provide an in-depth analysis of cell type-related gene signatures and transcription factor markers, as well as sexual dimorphism, across the whole animal. Analysis of common cell types between tissues, such as blood and muscle cells, reveals rare cell types and tissue-specific subtypes. This atlas provides a valuable resource for the Drosophila community and serves as a reference to study genetic perturbations and disease models at single-cell resolution.

The organic–inorganic composites F70-TiO2, based on fullerene with carboxyl group derivatives and TiO2 semiconductor, have been designed and constructed to become an optical-functional photocatalyst via the facile sol–gel method. The composite photocatalyst obtained shows excellent photocatalytic activity for the high-efficiency conversion of benzylamine (BA) to N-benzylidene benzylamine (NBBA) with air pressure at a normal temperature under visible light irradiation. By optimizing the composition, the composites with the 1:15 mass ratio of F70 and TiO2, denoted as F70-TiO2(1:15), demonstrated the highest reaction efficiency for benzylamine (>98% conversion) to N-benzylidene benzylamine (>93% selectivity) in this study. However, pure TiO2 and fullerene derivatives (F70) exhibit decreased conversion (56.3% and 89.7%, respectively) and selectivity (83.8% and 86.0%, respectively). The UV–vis diffuse reflectance spectra (DRS) and Mott–Schottky experiment's results indicate that the introduction of fullerene derivatives into anatase TiO2 would greatly broaden the visible light response range and adjust the energy band positions of the composites, enhancing the sunlight utilization and promoting the photogenerated charge (e−-h+) separation and transfer. Specifically, a series of results on the in situ EPR tests and the photo-electrophysical experiment indicate that the separated charges from the hybrid could effectively activate benzylamine and O2 to accelerate the formation of active intermediates, and then couple with free BA molecules to form the desired production of N-BBA. The effective combination, on a molecular scale, between fullerene and titanium dioxide has provided a profound understanding of the photocatalysis mechanism. This work elaborates and makes clear the relationship between the structure and the performance of functional photocatalysts. [ABSTRACT FROM AUTHOR]