PXD059199

PXD059199 is an original dataset announced via ProteomeXchange.

Title	Mitochondrial unfolding protein CLPX is required for oocyte competence during ovarian aging
Description	Ovarian aging has reproductive and overall health implications with increased infertility, miscarriage rates, and adverse outcomes associated with menopause. Mitochondrial dysfunction is one of the main mechanisms of female reproductive aging. Mitochondrial protein homeostasis maintains mitochondrial function and globally dysregulated unfolded mitochondrial protein response accelerates reproductive aging. However, the role of oocyte mitochondrial proteostasis in determining oocyte quality is unknown. ClpX (Caseinolytic Protease X) is a mitochondrial protein unfoldase that maintains mitochondrial protein homeostasis. In this study, we uncovered that Clpx deficiency, either through genetic ablation or natural decline with aging in mice, leads to the disrupted mitochondrial proteostasis in oocytes. Oocyte-specific knockout of Clpx impaired oocyte quality and developmental competence, thereby leading to female subfertility. Transcriptomic and micro-proteomic analyses of Clpx null oocytes revealed dysregulated mitochondrial function, protein processing and meiosis. Notably, Clpx deficiency promoted PGD2 synthesis and DP1/PKA/cAMP and DP2/AKT/mTOR signaling pathways by upregulating Ptgds. The PGD2 synthesis inhibitor AT-56 restored the developmental competence of Clpx knockout and aged oocytes. Our findings indicate the pivotal role of oocyte mitochondrial proteostasis in the regulation of oocyte quality with aging and pave the way for future investigations assessing the potential therapeutic value of these pathways to improve infertility treatment outcomes.
HostingRepository	iProX
AnnounceDate	2024-12-24
AnnouncementXML	Submission_2025-06-03_20:09:15.312.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Renwu Hua
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-23 19:40:27	ID requested
⏵ 1	2025-06-03 20:09:15	announced

Dataset with its publication pending

submitter keyword: Proteomics, Clpx knockout, oocytes

Tianren Wang
contact affiliation	The University of Hongkong - Shenzhen Hospital
contact email	wtrcmu@126.com
lab head
Renwu Hua
contact affiliation	The University of Hongkong - Shenzhen Hospital
contact email	huarenwu1994@163.com
dataset submitter

iProX dataset URI