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

PTEN-L suppresses GSDME-dependent pyroptosis by dephosphorylating and inactivating Parkin, preventing mitochondrial-driven inflammatory cell death.

• Why it matters: Understanding how mitochondrial damage triggers pyroptosis is crucial for developing therapies against inflammatory diseases and cell death-related conditions. The signaling pathways connecting mitochondrial dysfunction to pyroptosis remain poorly defined, limiting targeted interventions.
• What they did: The study examined the role of PTEN-L in regulating the PINK1-Parkin pathway and pyroptosis, using molecular and cellular approaches to analyze Parkin activity, mitochondrial dynamics, and cell death markers.
• The result: PTEN-L inhibits pyroptosis by dephosphorylating Parkin, stabilizing MCL-1, and blocking the downstream BAX/BAK-caspase-3-GSDME cascade, revealing a new regulatory mechanism linking mitochondrial quality control to inflammatory cell death.