HSP90 deficiency promotes cholesteryl ester accumulation in lipid droplets via endocytosis of low-density lipoprotein.

ABSTRACT: The size and number of lipid droplets (LDs), as intracellular lipids storage organelles, are closely correlated to lipid metabolism. However, the regulation of lipid metabolism is still unclear. Here, based on changes in three LD phenotypic indicators, including LD number, average LD area, and total LD amount in a cell, we establish an imaging-based high-throughput screen on a compound library. We identify that HSP90 inhibitors effectively promote lipid accumulation, as demonstrated by the increased total amount of cellular LDs. Both gene silencing and functional inhibition of HSP90 result in LD accumulation. This LD phenotype induced by HSP90 knockdown is autophagy-independent and requires functional lysosomal pathway. We further identify cholesteryl ester (CE) as the major lipid class ac

SUBMITTER: Ma C 

PROVIDER: S-EPMC12328731 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature