PXD083090

PXD083090 is an original dataset announced via ProteomeXchange.

Title	Multi-omics analysis reveals that Aβ42- Me3 co-aggregation induces mitophagy blockade in early stages of Alzheimer’s disease
Description	Mitochondrial dysfunction is one of the earliest hallmarks of Alzheimer’s disease (AD), but the association of amyloid-β (Aβ) toxicity with mitochondrial dysfunction remains largely elusive. Here, we explored early-stage AD pathogenic mechanisms in APP/PS1 mice and neuronal cells, and identified malic enzyme 3 (Me3) as a critical bridge linking Aβ aggregation to mitochondrial dysfunction. Me3 involved in the tricarboxylic acid (TCA) cycle was consistently upregulated during super early (month 3) and early stage (month 6) of AD. The upregulation of Me3 served as a compensation response to the TCA cycle disruption by Aβ aggregation. Under pathological conditions, Me3 aggregated in mitochondria and co-localized with Aβ aggregates, leading to excessive reactive oxygen species (ROS) production and mitophagy blockage. The hydrogen-deuterium exchange and cross-linking mass spectrometry further confirmed the interaction between Me3 and Aβ, resulting in the binding of Aβ42 to the catalytic domain of Me3, thereby inhibiting Me3 catalytic function. Knockdown of Me3 in neuronal cells attenuated ROS accumulation, normalized mitochondrial morphology, and rescued mitophagy blockage. Our findings highlight the great potential of Me3 as a therapeutic target for early intervention against AD.
HostingRepository	iProX
AnnounceDate	2026-08-20
AnnouncementXML	Submission_2026-08-24_18:25:50.450.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xin Liu
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2026-08-24 18:24:51	ID requested
⏵ 1	2026-08-24 18:25:50	announced

Dataset with its publication pending

submitter keyword: Alzheimer’s disease, proteomics, mitophagy, β-amyloid, malic enzyme 3

Xin Liu
contact affiliation	Huazhong University of Science and Technology
contact email	xliu@mail.hust.edu.cn
lab head
Xin Liu
contact affiliation	Huazhong University of Science and Technology
contact email	635877739@qq.com
dataset submitter

iProX dataset URI