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Sensitivity To Lysosome-Dependent Cell Death Is Directly Regulated By Lysosomal Cholesterol Content, Hanna Appelqvist, Linnea Sandin, Karin Bjornstrom, Paul Saftig, Brett Garner, Karin Ollinger, Katarina Kagedal

Faculty of Science, Medicine and Health - Papers: part A

Alterations in lipid homeostasis are implicated in several neurodegenerative diseases, although the mechanisms responsible are poorly understood. We evaluated the impact of cholesterol accumulation, induced by U18666A, quinacrine or mutations in the cholesterol transporting Niemann-Pick disease type C1 (NPC1) protein, on lysosomal stability and sensitivity to lysosome-mediated cell death. We found that neurons with lysosomal cholesterol accumulation were protected from oxidative stress-induced apoptosis. In addition, human fibroblasts with cholesterol-loaded lysosomes showed higher lysosomal membrane stability than controls. Previous studies have shown that cholesterol accumulation is accompanied by the storage of lipids such as sphingomyelin, glycosphingolipids and sphingosine and an up …