PXD045298

PXD045298 is an original dataset announced via ProteomeXchange.

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	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:05:37.641.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD045298
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Jinsoo Seo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

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.

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]

submitter keyword: mitophagy, lysosomal cholesterol accumulation,ApoE4, glucose metabolism, human astrocytes

Jinsoo Seo
contact affiliation	Department of Brain Sciences, Daegu Gyeongbuk Institute of Science & Technology
contact email	jsseo@dgist.ac.kr
lab head
Jinsoo Seo
contact affiliation	DGIST
contact email	jsseo@dgist.ac.kr
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/09/PXD045298

PRIDE project URI

• PRIDE
  1. PXD045298
     1. Label: PRIDE project
     2. Name: ApoE4-dependent lysosomal cholesterol accumulation impairs mitochondrial homeostasis and oxidative phosphorylation in human astrocytes