PXD081568-1

PXD081568 is an original dataset announced via ProteomeXchange.

Title	The original datas of proteomics about subject called PTEN-L-mediated dephosphorylation of Parkin couples inhibition of mitophagy to suppression of GSDME-dependent pyroptosis
Description	Hela YFP-Parkin Vector/PTEN-L cell lysates following treatment with 20 μM CCCP for 18 h; Mitochondrial dysfunction serves as a potent trigger of inflammatory cell death; however, the precise signaling pathways linking mitochondrial damage to pyroptosis remain incompletely understood. Here, we identify a previously unrecognized pathway in which mitochondrial depolarization activates the PINK1-Parkin axis to drive GSDME-mediated pyroptosis, a process negatively regulated by the phosphatase PTEN-L. Upon activation, Parkin promotes the ubiquitination and proteasomal degradation of MCL-1, facilitating mitochondrial translocation and activation of BAX. This triggers cytochrome c release, caspase-3 activation, and subsequent cleavage and plasma membrane targeting of GSDME, ultimately leading to pyroptotic cell death. Conversely, PTEN-L functions as a master negative regulator that counteracts Parkin through a dual mechanism: it directly dephosphorylates and inactivates Parkin, while competitively disrupting the Parkin-MCL-1 ligase-substrate complex. This coordinated action not only suppresses mitophagy but also stabilizes MCL-1, thereby inhibiting the downstream BAX/BAK–caspase-3–GSDME cascade and subsequent pyroptosis. Thus, our findings reveal a phosphorylation-dependent regulatory switch centered on Parkin that functionally couples mitophagy regulation to GSDME-dependent pyroptosis, delineating a novel mitochondrial signaling pathway that integrates organelle quality control with cellular fate decisions under stress conditions.
HostingRepository	iProX
AnnounceDate	2026-07-23
AnnouncementXML	Submission_2026-07-23_20:06:03.847.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Chenghao Yan
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2026-07-23 20:05:14	ID requested
⏵ 1	2026-07-23 20:06:04	announced

Dataset with its publication pending

submitter keyword: PINK1-Parkin axis, mitophagy, PTEN-L, GSDME-dependent pyroptosis, mitochondrial stress

Liming Wang
contact affiliation	School of Biomedical Sciences, Hunan University
contact email	wangliming@hnu.edu.cn
lab head
Chenghao Yan
contact affiliation	School of Biomedical Sciences, Hunan University
contact email	ych9702@hnu.edu.cn
dataset submitter

iProX dataset URI