{"database":"iProX","file_versions":[],"scores":null,"additional":{"omics_type":["Proteomics"],"submitter":["Liming Wang"],"species":["Homo Sapiens"],"full_dataset_link":["http://www.iprox.org/page/project.html?id=IPX0018613000"],"submitter_email":["wangliming@hnu.edu.cn"],"submitter_affiliation":["School of Biomedical Sciences, Hunan University"],"sample_protocol":[""],"repository":["iProX"],"data_protocol":[""],"additional_accession":[]},"is_claimable":false,"name":"PTEN-L-mediated dephosphorylation of Parkin couples inhibition of mitophagy to suppression of GSDME-dependent pyroptosis（2）","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.","dates":{"publication":"Mon Jul 27 00:00:00 GMT+01:00 2026"},"accession":"PXD081677","cross_references":{"TAXONOMY":["9606"]}}