RT Journal Article
SR Electronic
T1 High lumenal chloride in the lysosome is critical for lysosome function
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 141788
DO 10.1101/141788
A1 Kasturi Chakraborty
A1 KaHo Leung
A1 Yamuna Krishnan
YR 2017
UL http://biorxiv.org/content/early/2017/05/24/141788.abstract
AB Lysosomes are organelles responsible for the breakdown and recycling of cellular machinery. Dysfunctional lysosomes give rise to lysosomal storage disorders as well as common neurodegenerative diseases. Here, we use a DNA-based, fluorescent chloride reporter to measure lysosomal chloride in Caenorhabditis elegans as well as murine and human cell culture models of lysosomal diseases. We find that the lysosome is highly enriched in chloride, and that chloride reduction correlates directly with a loss in the degradative function of the lysosome. In nematodes and mammalian cell culture models of diverse lysosomal disorders, where previously only lysosomal pH dysregulation has been described, massive reduction of lumenal chloride is observed that is ~104-fold greater than the accompanying pH change. Reducing chloride within the lysosome impacts Ca2+ release from the lysosome and impedes the activity of specific lysosomal enzymes indicating a broader role for chloride in lysosomal function. −149 words.