Autophagosome–lysosome fusion is independent of V-ATPase-mediated acidification

Caroline Mauvezin, Péter Nagy, Gábor Juhász and Thomas P. Neufeld ()
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Caroline Mauvezin: Cell Biology and Development, University of Minnesota
Péter Nagy: Cell and Developmental Biology, Eötvös Loránd University
Gábor Juhász: Cell and Developmental Biology, Eötvös Loránd University
Thomas P. Neufeld: Cell Biology and Development, University of Minnesota

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: 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 Ca2+ 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.

Date: 2015
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DOI: 10.1038/ncomms8007

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