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- Title
PINK1 Defect Causes Mitochondrial Dysfunction, Proteasomal Deficit and α-Synuclein Aggregation in Cell Culture Models of Parkinson's Disease.
- Authors
Wencheng Liu; Vives-Bauza, Cristofol; Acín-Peréz, Rebeca; Yamamoto, Ai; Yingcai Tan; Yanping Li; Magrané, Jordi; Stavarache, Mihaela A.; Shaffer, Sebastian; Chang, Simon; Kaplitt, Michael G.; Huang, Xin-Yun; Beal, M. Flint; Manfredi, Giovanni; Chenjian Li
- 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 a-synclein aggregation. Our results indicate that it will be important to delineate the relationship between mitochondrial functional deficits, proteasome dysfunction and a-synclein aggregation.
- Subjects
MITOCHONDRIAL pathology; CELL culture; PARKINSON'S disease; SUCROSE; CYTOLOGICAL techniques; MATHEMATICAL complexes
- Publication
PLoS ONE, 2009, Vol 4, Issue 2, p1
- ISSN
1932-6203
- Publication type
Academic Journal
- DOI
10.1371/journal.pone.0004597