Acute accumulation of free cholesterol induces the degradation of perilipin 2 and Rab18-dependent fusion of ER and lipid droplets in cultured human hepatocytes

Asami Makino, Françoise Hullin-Matsuda, Motohide Murate, Mitsuhiro Abe, Nario Tomishigec, Mitsunori Fukuda, Shizuya Yamashita, Toyoshi Fujimoto, Hubert Vidal, Michel Lagarde, Isabelle Delton, Toshihide Kobayashi

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3293-3304
Number of pages12
JournalMolecular Biology of the Cell
Volume27
Issue number21
DOIs
Publication statusPublished - 2016 Nov 1

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