Cleaving PINK1 or PGAM5? Involvement of PARL in Methamphetamine-Induced Excessive Mitophagy and Neuronal Necroptosis.

ABSTRACT:

Background

Methamphetamine (Meth) is a potent psychoactive stimulant that triggers complex neurotoxicity characterized by autophagy-associated neuronal death. However, the potential mechanisms remain poorly understood. This study aimed to decipher the Meth-induced neuronal necroptosis involving mitochondrial defect-initiated excessive mitophagy caused by aberrant presenilin-associated rhomboid-like (PARL) cleavage of PTEN-induced kinase 1 (PINK1) and phosphoglycerate mutase family member 5 (PGAM5).

Methods and results

With the transcriptome analysis, Meth exposure significantly affected autophagy, mitophagy, and necroptosis pathways; meanwhile, the proteomic analysis revealed a marked decline in the level of PARL, which led to an imbalance in intramembrane proteolysis of PIN

SUBMITTER: An D 

PROVIDER: S-EPMC11865887 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature