PTEN-L inhibits mitophagy and GSDME-dependent pyroptosis via Parkin dephosphorylation

ABSTRACT: Mitochondrial dysfunction is 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 counterac

SUBMITTER: Liming Wang 

PROVIDER: S-SCDT-10_1038-S44319-026-00957-4 | biostudies-other |

REPOSITORIES: biostudies-other