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 Celljournal_title
Molecular biology of the cellauthors
Makino A,Hullin-Matsuda F,Murate M,Abe M,Tomishige N,Fukuda M,Yamashita S,Fujimoto T,Vidal H,Lagarde M,Delton I,Kobayashi Tdoi
10.1091/mbc.E15-10-0730subject
Has Abstractpub_date
2016-11-01 00:00:00pages
3293-3304issue
21eissn
1059-1524issn
1939-4586pii
mbc.E15-10-0730journal_volume
27pub_type
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