PXD072323

PXD072323 is an original dataset announced via ProteomeXchange.

Title	Klotho-derived peptide 1 protects against acute kidney injury by directly targeting mitochondrial ATAD3A
Description	Acute kidney injury (AKI) is a clinical syndrome associated with severe morbidity and high mortality, for which there are currently no effective therapies. Aging, a state of Klotho protein deficiency, is an independent and prominent risk factor for AKI development and progression. Here we report that Klotho-derived peptide 1 (KP1), a small peptide that recapitulates the renoprotective potential of Klotho, effectively protected against AKI in mouse models induced by either cisplatin or ischemia-reperfusion injury. KP1 treatment improved kidney function, ameliorated structural damage, inhibited tubular cell apoptosis, and preserved mitochondrial integrity in both models. Mechanistically, KP1 could enter into kidney proximal tubular epithelial cells via endocytosis, directly targeted the mitochondrial protein ATPase family AAA domain-containing protein 3A (ATAD3A), and prevented its degradation and preserved its function. By interacting with the hypoxia inducible gene 1 (HIG1) domain family member 2A (HIGD2A) and maintaining its expression and function within the mitochondria, ATAD3A prevented cytochrome c release and inhibited caspase activation following injury, thereby alleviating renal tubular cell apoptosis. Collectively, these studies demonstrate that KP1 is a promising therapeutic for AKI by directly targeting and preserving mitochondrial integrity. Our findings also lay the groundwork for developing novel therapeutic strategies to treat diseases associated with mitochondrial dysfunction.
HostingRepository	iProX
AnnounceDate	2025-12-22
AnnouncementXML	Submission_2026-08-05_21:46:43.718.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xiaoyao Zhang
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606; scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive; Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-22 18:09:28	ID requested
⏵ 1	2026-08-05 21:46:44	announced

Dataset with its publication pending

submitter keyword: AKI, KP1, Klotho, apoptosis, ATAD3A, mitochondrial dysfunction

Youhua Liu
contact affiliation	Southern Medical University
contact email	liuyh@smu.edu.cn
lab head
Xiaoyao Zhang
contact affiliation	Southern Medical University
contact email	799012440@qq.com
dataset submitter

iProX dataset URI