Transmembrane Parkinson's disease mutation of PINK1 leads to altered mitochondrial anchoring.

ABSTRACT: Parkinson's disease is a devastating neurodegenerative disease resulting from the death of dopaminergic neurons in the substantia nigra pars compacta of the midbrain. Familial and sporadic forms of the disease have been linked to mitochondrial dysfunction. Pathology has been identified with mutations in the PARK6 gene encoding PTEN-induced kinase 1 (PINK1), a quality control protein in the mitochondria. Disease-associated mutations at the transmembrane (TM) region of PINK1 protein were predicted to disrupt the cleavage of the TM region by the PARL (presenilin-associated rhomboid-like) protease at the inner mitochondrial membrane. Here, using microscopy, kinetic analysis, and molecular dynamics simulations, we analyzed three Parkinson's disease-associated TM mutations; PINK1-C92F, PINK1-R98

SUBMITTER: Brassard R 

PROVIDER: S-EPMC11910106 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature