RRC ID 48716
Author Makino A, Hullin-Matsuda F, Murate M, Abe M, Tomishige N, Fukuda M, Yamashita S, Fujimoto T, Vidal H, Lagarde M, Delton I, Kobayashi T.
Title Acute accumulation of free cholesterol induces the degradation of perilipin 2 and Rab18-dependent fusion of ER and lipid droplets in cultured human hepatocytes.
Journal Mol Biol Cell
Abstract Dysregulated hepatic cholesterol homeostasis with free cholesterol accumulation in the liver is relevant to the pathogenesis of nonalcoholic steatohepatitis, contributing to the chronicity of liver toxicity. Here we examined the effect of free cholesterol accumulation on the morphology and biochemical properties of lipid droplets (LDs) in cultured hepatocytes. Acute free cholesterol accumulation induced the fusion of LDs, followed by degradation of the coat protein of LDs, perilipin 2 (PLIN2; also called adipophilin or adipose differentiation-related protein), and association of apolipoprotein B 100 (ApoB 100) to LDs. The degradation of PLIN2 was inhibited by inhibitors of ubiquitination, autophagy, and protein synthesis. The results indicate that association of ApoB 100 with LDs is dependent on the activity of low-molecular weight GTP-binding protein Rab18 and highlight the role of LDs as targets of free cholesterol toxicity in hepatocytes.
Volume 27(21)
Pages 3293-3304
Published 2016-11-1
DOI 10.1091/mbc.E15-10-0730
PII mbc.E15-10-0730
PMID 27582390
PMC PMC5170862
MeSH Apolipoprotein B-100 / metabolism Apolipoprotein B-100 / physiology Carrier Proteins / metabolism Cell Culture Techniques Cholesterol / metabolism* Cholesterol / physiology Endoplasmic Reticulum / pathology Hepatocytes / metabolism Humans Lipid Droplets / metabolism* Lipid Droplets / physiology* Lipid Metabolism Lipids / chemistry Liver / metabolism Membrane Proteins / metabolism Perilipin-2 / metabolism Phosphoproteins / metabolism rab GTP-Binding Proteins
IF 3.791
Times Cited 9
DNA material pSpCas9(BB)-2A-puro-ACAT1 sgRNA (RDB14697) pSpCas9(BB)-2A-puro-ACAT2 sgRNA (RDB14698) pDEST/mCherry-Rab18 (RDB14699) pDEST/mCherry-Rab18 Q67L (RDB14700) pDEST/mCherry-Rab18 S22N (RDB14701).