THE ROLE OF ROS AND VDAC1 IN PARKIN/PINK1-MEDIATED MITOPHAGY

Abstract

DEFECT IN MITOPHAGY HAS BEEN DEMONSTRATED TO BE IMPLICATED IN THE PATHOGENESIS OF PARKINSON'S DISEASE. THE WELL-ESTABLISHED MODEL SUGGESTS THAT PINK1 ACCUMULATES ON THE OUTER MEMBRANE OF DAMAGED MITOCHONDRIA, SUBSEQUENTLY RECRUITING PARKIN. HERE I SHOW THAT UPON CCCP TREATMENT, THE ACCUMULATION OF PINK1 IS NEITHER NECESSARY NOR SUFFICIENT FOR PARKIN TRANSLOCATION TO MITOCHONDRIA. MOREOVER, I FOUND THAT REACTIVE OXYGEN SPECIES (ROS) SCAVENGERS FAILED TO RESCUE CCCP-INDUCED PARKIN TRANSLOCATION DUE TO ITS INEFFICIENCY. IMPORTANTLY, PINK1-DEPENDENT PARKIN TRANSLOCATION TO MITOCHONDRIA CAN BE REVERSED BY THE TREATMENT OF TWO DIFFERENT ROS SCAVENGERS IN RESPONSE TO EITHER THE CCCP TREATMENT OR VDAC1 OVEREXPRESSION. IN ADDITION, PHOSPHORYLATION OF VDAC1 MAY BE CRUCIAL FOR ITS UBIQUITINATION MEDIATED BY PARKIN DURING MITOPHAGY. THUS, MY DATA HIGHLIGHT THE IMPORTANCE OF THE PRESENCE RATHER THAN THE ACCUMULATION OF PINK1 IN PARKIN RECRUITMENT TO MITOCHONDRIA AND ACCENTUATE THE NECESSITY OF FINE