Transmembrane domain switching controls PINK1 import and fate in mitochondria - PubMed
3 hours ago
- #Mitochondria
- #Parkinson's Disease
- #Protein Import
- PINK1 kinase is imported into mitochondria under normal conditions via membrane-potential-driven inner membrane penetration, then cleaved by PARL before retro-translocation and degradation.
- In compromised mitochondria with reduced membrane potential, PINK1 remains on the surface, activates Parkin recruitment, and triggers mitophagy.
- A third pathway involves PINK1 import into the mitochondrial matrix, determined by its transmembrane domain (TMD) structural plasticity—forming either an α-helix or α/β-hybrid.
- The α-helical TMD interacts with ROMO1/Tim17 for translocation into the matrix, while the α/β-hybrid engages PARL for cleavage and retro-translocation.
- These findings expand PINK1's role beyond a damage sensor, suggesting involvement in healthy mitochondrial function and potential relevance to Parkinson's disease.