Spatial Regulation of Lysosomal Vesicle Acidification Along the Axon via mRAVE-Dependent v-ATPase Assembly.

ABSTRACT: Lysosomal acidification is essential for neuronal homeostasis, supporting degradative clearance and metabolic signaling in all neuronal domains. Yet, how lysosomal acidification is spatially regulated within neurons remains unclear. Here, we show that assembly of the membrane-embedded V₀ and cytosolic V₁ domains of the vacuolar H⁺-ATPase (v-ATPase) - the proton pump that drives lysosomal acidification - governs spatial and functional lysosome diversity. In non-neuronal cells, V₁-V₀ association is higher in perinuclear lysosomes, correlating with increased acidity of this population. In neurons, axonal V₀-positive vesicles move bidirectionally, whereas V₁-V₀-positive vesicles move almost exclusively in t

SUBMITTER: Verma S 

PROVIDER: S-EPMC12776041 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature