PUBLICATION
Cholesterol transport through lysosome-peroxisome membrane contacts
- Authors
- Chu, B.B., Liao, Y.C., Qi, W., Xie, C., Du, X., Wang, J., Yang, H., Miao, H.H., Li, B.L., Song, B.L.
- ID
- ZDB-PUB-170214-198
- Date
- 2015
- Source
- Cell 161: 291-306 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Adrenoleukodystrophy/metabolism
- Animals
- Zebrafish
- Biological Transport
- Humans
- Genome-Wide Association Study
- Lysosomes/metabolism*
- Cholesterol/metabolism*
- Phosphatidylinositol 4,5-Diphosphate/metabolism
- Peroxisomal Disorders/metabolism
- Peroxisomal Disorders/pathology
- RNA, Small Interfering/metabolism*
- Amphotericin B/pharmacology
- Synaptotagmins/metabolism
- Mice
- Peroxisomes/metabolism*
- ATP-Binding Cassette Transporters/metabolism
- PubMed
- 25860611 Full text @ Cell
Citation
Chu, B.B., Liao, Y.C., Qi, W., Xie, C., Du, X., Wang, J., Yang, H., Miao, H.H., Li, B.L., Song, B.L. (2015) Cholesterol transport through lysosome-peroxisome membrane contacts. Cell. 161:291-306.
Abstract
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)P2 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.
Errata / Notes
This article is corrected by ZDB-PUB-220906-231 .
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping