Massive Accumulation of Sphingomyelin Affects the Lysosomal and Mitochondria Compartments and Promotes Apoptosis in Niemann-Pick Disease Type A.

ABSTRACT: Niemann-Pick type A disease (NPA) is a rare lysosomal storage disorder caused by mutations in the gene coding for the lysosomal enzyme acid sphingomyelinase (ASM). ASM deficiency leads to the consequent accumulation of its uncatabolized substrate, the sphingolipid sphingomyelin (SM), causing severe progressive brain disease. To study the effect of the aberrant lysosomal accumulation of SM on cell homeostasis, we loaded skin fibroblasts derived from a NPA patient with exogenous SM to mimic the levels of accumulation characteristic of the pathological neurons. In SM-loaded NPA fibroblasts, we found the blockage of the autophagy flux and the impairment of the mitochondrial compartment paralleled by the altered transcription of several genes, mainly belonging to the electron transport chain ma

SUBMITTER: Carsana EV 

PROVIDER: S-EPMC9293875 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature