The lysosomal storage disorder Neimann-Pick Disease is caused by mutations in the transporters that remove cholesterol from the lysosomes. Lysosomal cholesterol is the signal for mTORC1, so this disorder may progress via the aberrant growth phenotype of stimulating mTORC1. #BAAM
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Lysosomal immunoprecipitation mass spec shows that NPC lysosomes are less able to degrade protein fragments.
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Treat cells with Torin1, a competitive inhibitor of mTORC1, restores autophagy ability; rapamycin, which is an allosteric inhibitor, has a minimal effect.
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NPC-diseased cells have less autophagy and more fragmented mitochondria; Torin1 fixes it.
1:37 PM - 5 Dec 2019
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