Association of autophagy with cholesterol-accumulated compartments in Niemann-Pick disease type C cells.

Niemann-Pick disease type C (NPC) is an autosomal recessive disease most commonly caused by a mutation of NPC1, resulting in the accumulation of cholesterol in late endosomes or lysosomes. In this study, we examined whether an abnormality of autophagy is involved in the pathogenesis of NPC and how cholesterol accumulation participates in this process, using both a U18666A-induced NPC model and NPC1-deficient Chinese hamster ovary cells. In these cells, an increase in the level of the microtubule-associated protein 1 light chain 3 (LC3-II) was demonstrated by Western blotting. An increase in the number of granular LC3-positive structures that colocalized with filipin-labeled accumulated cholesterol was also observed in morphological studies. Cholesterol depletion inhibited the formation of granular LC3-positive structures that colocalized with filipin-labeled cholesterol, and instead promoted the formation of ring-shaped LC3-positive filipin-negative structures in U18666A-treated cells. These results demonstrate the close association of the accumulation of LC3 with accumulated cholesterol in NPC cells.