RRC ID 36313
Author Mauvezin C, Nagy P, Juhász G, Neufeld TP.
Title Autophagosome-lysosome fusion is independent of V-ATPase-mediated acidification.
Journal Nat Commun
Abstract The ATP-dependent proton pump V-ATPase ensures low intralysosomal pH, which is essential for lysosomal hydrolase activity. Based on studies with the V-ATPase inhibitor BafilomycinA1, lysosomal acidification is also thought to be required for fusion with incoming vesicles from the autophagic and endocytic pathways. Here we show that loss of V-ATPase subunits in the Drosophila fat body causes an accumulation of non-functional lysosomes, leading to a block in autophagic flux. However, V-ATPase-deficient lysosomes remain competent to fuse with autophagosomes and endosomes, resulting in a time-dependent formation of giant autolysosomes. In contrast, BafilomycinA1 prevents autophagosome-lysosome fusion in these cells, and this defect is phenocopied by depletion of the Ca(2+) pump SERCA, a secondary target of this drug. Moreover, activation of SERCA promotes fusion in a BafilomycinA1-sensitive manner. Collectively, our results indicate that lysosomal acidification is not a prerequisite for fusion, and that BafilomycinA1 inhibits fusion independent of its effect on lysosomal pH.
Volume 6
Pages 7007
Published 2015-5-11
DOI 10.1038/ncomms8007
PII ncomms8007
Description FRT-linked mutants from the Bloomington Stock Center and Drosophila Genetic Resource Center (Kyoto, Japan)
PMID 25959678
PMC PMC4428688
MeSH Acids / metabolism* Animals Autophagy* / drug effects Drosophila melanogaster / drug effects Drosophila melanogaster / enzymology* Lysosomes / drug effects Lysosomes / metabolism* Lysosomes / ultrastructure Macrolides / pharmacology Membrane Fusion* / drug effects Models, Biological Phagosomes / drug effects Phagosomes / metabolism* Phagosomes / ultrastructure Protein Subunits / metabolism Sarcoplasmic Reticulum Calcium-Transporting ATPases / antagonists & inhibitors Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism Vacuolar Proton-Translocating ATPases / metabolism*
IF 12.353
Times Cited 39