Publication Type Academic Article
Authors Liu W, Vives-Bauza C, Acín-Peréz- R, Yamamoto A, Tan Y, Li Y, Magrané J, Stavarache M, Shaffer S, Chang S, Kaplitt M, Huang X, Beal M, Manfredi G, Li C
Journal PLoS One
Volume 4
Issue 2
Pagination e4597
Date Published 02/26/2009
ISSN 1932-6203
Keywords Mitochondria, Proteasome Endopeptidase Complex, Protein Kinases, alpha-Synuclein
Abstract Mutations in PTEN induced kinase 1 (PINK1), a mitochondrial Ser/Thr kinase, cause an autosomal recessive form of Parkinson's disease (PD), PARK6. Here, we report that PINK1 exists as a dimer in mitochondrial protein complexes that co-migrate with respiratory chain complexes in sucrose gradients. PARK6 related mutations do not affect this dimerization and its associated complexes. Using in vitro cell culture systems, we found that mutant PINK1 or PINK1 knock-down caused deficits in mitochondrial respiration and ATP synthesis. Furthermore, proteasome function is impaired with a loss of PINK1. Importantly, these deficits are accompanied by increased alpha-synclein aggregation. Our results indicate that it will be important to delineate the relationship between mitochondrial functional deficits, proteasome dysfunction and alpha-synclein aggregation.
DOI 10.1371/journal.pone.0004597
PubMed ID 19242547
PubMed Central ID PMC2644779
Back to Top