Diverse mitochondrial stresses activate PINK1-PRKN/parkin mitophagy by a unified mechanism - PubMed
4 hours ago
- #Mitochondrial Stress
- #Mitophagy
- #Parkinson Disease
- Mutations in PINK1 and PRKN/parkin are leading recessive causes of Parkinson disease (PD).
- PINK1 and PRKN form a mitophagy pathway for clearing damaged mitochondria from the cell.
- Diverse mitochondrial stressors activate the PINK1-PRKN pathway through a unified mechanism involving loss of mitochondrial membrane potential (MMP).
- MMP is required for PINK1 import into mitochondria, involving transfer between outer and inner mitochondrial membrane translocases (TOMM and TIMM23).
- Chronic disruption of the TIMM23 complex stabilizes active PINK1 in the TOMM complex, mimicking MMP loss.
- PINK1 primarily senses catastrophic drops in MMP, indicating a mitochondrion's inability to continue biogenesis.