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PXD065603

PXD065603 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	Lactylation of HSP90β disrupts HSP90β-APAF-1 interaction to mediate heat stress induced brain microvascular endothelial cell apoptosis
Description	Lysine lactylation (Kla) is a metabolite-sensing post-translational modification that bridges cellular metabolism to protein function. Here, we discover that heat stress triggers anaerobic glycolysis and lactate accumulation in brain microvascular endothelial cells (BMECs).Mechanistically, AARS1 catalyzes the transfer of lactate to HSP90β at lysine 275 (K275). Critically, this lactylation modification acts as a regulatory switch for the protective factor HSP90β, disrupting its interaction with apoptotic protease-activating factor 1 (APAF-1). This modification thereby compromises the protective function of HSP90β, liberating APAF-1 to activate the mitochondrial apoptosis pathway, resulting in blood-brain barrier (BBB) injury. Functional validation reveals that decreasing lactate production, overexpressing HSP90β lactylation-deficient mutant, or inhibiting AARS1 confers protection. These findings establish HSP90β-K275 lactylation as a metabolic switch that modulates protective mechanisms during heat-stress-induced cerebrovascular injury.
HostingRepository	iProX
AnnounceDate	2025-06-30
AnnouncementXML	Submission_2025-06-30_00:29:31.192.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jiao Qin
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-30 00:29:13	ID requested
⏵ 1	2025-06-30 00:29:31	announced

Publication List

Dataset with its publication pending

Keyword List

submitter keyword: Lactylation

Contact List

Yuhao Zou
contact affiliation	Department of Otolaryngology Head & Neck Surgery/Deep Underground Space Medical Center, West China Hospital
contact email	zouyuhaos@163.com
lab head
Jiao Qin
contact affiliation	Department of Otolaryngology Head & Neck Surgery/Deep Underground Space Medical Center, West China Hospital
contact email	1714096155@qq.com
dataset submitter

Full Dataset Link List

iProX dataset URI