Cholesterol transport through lysosome-peroxisome membrane contacts.
Open accessAbstract
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.
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Peroxisomes were proposed to function as hubs for the transfer of cholesterol to the ER for degradation.
“Alternatively, peroxisomes were proposed to function as hubs for the transfer of cholesterol to the ER for degradation (Chu et al., 2015; Yamashita et al., 2023).”
From The neurological pathology of peroxisomal ACBD5 deficiency – lessons from patients and mouse models (2025) · cites this paper as Chu et al., 2015
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The neurological pathology of peroxisomal ACBD5 deficiency – lessons from patients and mouse models
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“Key findings indicate that impaired peroxisome biogenesis redirected the microglial response during demyelination, expanding a pool of crystal-laden DMAMs deficient in debris clearance biogenesis factors disrupted sterol export, leading to intracellular sterol accumulation (44).”
- 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.
- Affiliations
- Chinese Academy of Sciences (CN)
- UNSW Sydney (AU)
- Henan Agricultural University (CN)
- Wuhan University (CN)
- Corresponding author
- Song, Bao-Liang
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 161
- Issue
- 2
- Pages
- 291-306
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1972926511
- Cited by
- 377
- References
- 1
- Citations by year
- 2026: 15 · 2025: 21 · 2024: 31 · 2023: 41 · 2022: 42 · 2021: 36 · 2020: 45 · 2019: 31 · 2018: 36 · 2017: 40 · 2016: 22 · 2015: 16
- FWCI
- 20.43
- Type
- journal article
- Language
- en
- Update notices
- erratum (2021-01-07)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Keywords
- intracellular cholesterol transport, peroxisomes, lysosomes, synaptotagmin VII, phosphatidylinositol 4,5-bisphosphate, LDL cholesterol, peroxisomal disorders, cholesterol accumulation
- MeSH terms
- Adrenoleukodystrophy, Amphotericin B, Animals, Biological Transport, Cholesterol, Humans, Lysosomes, Zebrafish, ATP-Binding Cassette Transporters, Peroxisomal Disorders, Phosphatidylinositol 4,5-Diphosphate, Peroxisomes, RNA, Small Interfering, Synaptotagmins, Mice, Genome-Wide Association Study
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