Cholesterol Transport through Lysosome-Peroxisome Membrane Contacts
文献类型：期刊论文
| 作者 | Chu, BB; Liao, YC; Qi, W; Xie, C; Du, XM; Wang, J; Yang, HY; Miao, HH; Li, BL; Song, BL |
| 刊名 | CELL
 |
| 出版日期 | 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 |
| 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. |
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