Lysosomal activity depends on TRPML1-mediated Ca²⁺ release coupled to incoming vesicle fusions.

ABSTRACT: The lysosomal cation channel TRPML1/MCOLN1 facilitates autophagic degradation during amino acid starvation based on studies involving long-term TRMPL1 modulation. Here we show that lysosomal activation (more acidic pH and higher hydrolase activity) depends on incoming vesicle fusions. We identify an immediate, calcium-dependent role of TRPML1 in lysosomal activation through promoting autophagosome-lysosome fusions and lysosome acidification within 10 to 20 min of its pharmacological activation. Lysosomes also become more fusion competent upon TRPML1 activation via increased transport of lysosomal SNARE proteins syntaxin 7 and VAMP7 by SNARE carrier vesicles. We find that incoming vesicle fusion is a prerequisite for lysosomal Ca²⁺ efflux that leads to acidification and hydrolyti

SUBMITTER: Bhattacharjee A 

PROVIDER: S-EPMC11599452 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature