PXD045298 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | ApoE4-dependent lysosomal cholesterol accumulation impairs mitochondrial homeostasis and oxidative phosphorylation in human astrocytes |
Description | Recent developments in genome sequencing have expanded the knowledge of genetic factors associated with late-onset Alzheimer’s disease (AD). Among them, genetic variant e4 of the APOE gene (ApoE4) confers the greatest disease risk. Dysregulated glucose metabolism is an early pathological feature of AD. Using isogenic ApoE3 and ApoE4 astrocytes derived from human-induced pluripotent stem cells, we find that ApoE4 increases glycolytic activity but impairs mitochondrial respiration in astrocytes. Ultrastructural and autophagic flux analyses show that ApoE4-induced cholesterol accumulation impairs lysosome-dependent removal of damaged mitochondria. Acute treatment with cholesterol-depleting agents restores autophagic activity, mitochondrial dynamics, and associated proteomes, and extended treatment rescues mitochondrial respiration in ApoE4 astrocytes. Taken together, our study provides a direct link between ApoE4-induced lysosomal cholesterol accumulation and abnormal oxidative phosphorylation. |
HostingRepository | PRIDE |
AnnounceDate | 2023-10-04 |
AnnouncementXML | Submission_2023-10-04_00:44:06.709.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD045298 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | JinsooSeo |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-09-12 03:28:56 | ID requested | |
1 | 2023-09-12 03:57:03 | announced | |
⏵ 2 | 2023-10-04 00:44:07 | announced | 2023-10-04: Updated project metadata. |
3 | 2023-11-14 09:05:45 | announced | 2023-11-14: Updated project metadata. |
Publication List
10.6019/PXD045298; |
Lee H, Cho S, Kim MJ, Park YJ, Cho E, Jo YS, Kim YS, Lee JY, Thoudam T, Woo SH, Lee SI, Jeon J, Lee YS, Suh BC, Yoon JH, Go Y, Lee IK, Seo J, ApoE4-dependent lysosomal cholesterol accumulation impairs mitochondrial homeostasis and oxidative phosphorylation in human astrocytes. Cell Rep, 42(10):113183(2023) [pubmed] |
Keyword List
submitter keyword: mitophagy, lysosomal cholesterol accumulation,ApoE4, glucose metabolism, human astrocytes |
Contact List
JinsooSeo |
contact affiliation | Department of Brain Sciences, Daegu Gyeongbuk Institute of Science & Technology |
contact email | jsseo@dgist.ac.kr |
lab head | |
JinsooSeo |
contact affiliation | DGIST |
contact email | jsseo@dgist.ac.kr |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD045298
- Label: PRIDE project
- Name: ApoE4-dependent lysosomal cholesterol accumulation impairs mitochondrial homeostasis and oxidative phosphorylation in human astrocytes