The Role of Autophagy in Phosphatidylglycerol Facilitated Cholesterol Clearance from the Endolysosomal System of NPC-1 Deficient Cells

Abstract

Niemann Pick Type C (NPC) Disease is a rare lysosomal storage disorder in which one of the genes that codes for either the NPC-1 or NPC-2 protein is mutated, causing cell lysosomes to accumulate cholesterol and lipids. Previous studies discovered that a unique late endosomal/lysosomal phospholipid, lysobisphosphatidic acid (LPBA), is involved in cholesterol clearance from late endosomes. It has also been shown that exogenous treatment of the NPC-1 deficient cells with LBPA’s precursor, phosphatidylglycerol (PG), leads to LBPA enrichment and subsequent endolysosomal cholesterol clearance. Autophagy is a mechanism of cellular clearance in the endolysomal system and we are interested to see if it is a partial route in cholesterol clearance during PG treatment of NPC-1 deficient cells. To do so, we silenced the gene that codes for an essential protein in the autophagy pathway, making the cells autophagy deficient. We then treated the cells with PG, measured the amount of cholesterol clearance in those cells, and compared it to cells with normal autophagy. We found significantly less cholesterol clearance by PG in cells with defective autophagy, confirming that autophagy is involved as a partial route in cholesterol clearance during PG treatment, but not enough of a difference to conclude that it is a major underlying mechanism.

https://doi.org/10.14713/arestyrurj.v1i3.171
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Copyright (c) 2021 Tamara Allada, Olga Ilnytska , Judith Storch