Cholesterol Transport through Lysosome-Peroxisome Membrane Contacts

	Cholesterol Transport through Lysosome-Peroxisome Membrane Contacts
	Chu, BB; Liao, YC; Qi, W; Xie, C; Du, XM; Wang, J; Yang, HY; Miao, HH; Li, BL; Song, BL
刊名	CELL
	2015
卷号	161 期号:2 页码:291-306
通讯作者	Song, BL (reprint author), Wuhan Univ, Inst Adv Studies, Coll Life Sci, Wuhan 430072, Peoples R China.,blsong@whu.edu.cn
英文摘要	Cholesterol is dynamically transported among organelles, which is essential for multiple cellular functions. However, the mechanism underlying intracellular cholesterol transport has remained largely unknown. We established an amphotericin B-based assay enabling a genome-wide shRNA screen for delayed LDL-cholesterol transport and identified 341 hits with particular enrichment of peroxisome genes, suggesting a previously unappreciated pathway for cholesterol transport. We show dynamic membrane contacts between peroxisome and lysosome, which are mediated by lysosomal Synaptotagmin VII binding to the lipid PI(4,5)P-2 on peroxisomal membrane. LDL-cholesterol enhances such contacts, and cholesterol is transported from lysosome to peroxisome. Disruption of critical peroxisome genes leads to cholesterol accumulation in lysosome. Together, these findings reveal an unexpected role of peroxisome in intracellular cholesterol transport. We further demonstrate massive cholesterol accumulation in human patient cells and mouse model of peroxisomal disorders, suggesting a contribution of abnormal cholesterol accumulation to these diseases.
学科主题	Biochemistry & Molecular Biology ; Cell Biology
类目[WOS]	Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]	SYNAPTOTAGMIN-VII ; BILE-ACID ; ADRENOLEUKODYSTROPHY ; CELLS ; GENE ; MICE ; HOMEOSTASIS ; ENDOCYTOSIS ; EXOCYTOSIS ; PATHWAY
收录类别	SCI
语种	英语
WOS记录号	WOS:000352708300022
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/15]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Chu, BB,Liao, YC,Qi, W,et al. Cholesterol Transport through Lysosome-Peroxisome Membrane Contacts[J]. CELL,2015,161(2):291-306.
APA	Chu, BB.,Liao, YC.,Qi, W.,Xie, C.,Du, XM.,...&Song, BL.(2015).Cholesterol Transport through Lysosome-Peroxisome Membrane Contacts.CELL,161(2),291-306.
MLA	Chu, BB,et al."Cholesterol Transport through Lysosome-Peroxisome Membrane Contacts".CELL 161.2(2015):291-306.