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

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.

journal_name

Mol Biol Cell

authors

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

doi

10.1091/mbc.E15-10-0730

subject

Has Abstract

pub_date

2016-11-01 00:00:00

pages

3293-3304

issue

21

eissn

1059-1524

issn

1939-4586

pii

mbc.E15-10-0730

journal_volume

27

pub_type

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