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PMID: 19242547 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

PINK1 defect causes mitochondrial dysfunction, proteasomal deficit and alpha-synuclein aggregation in cell culture models of Parkinson's disease.

PloS one ·Vol. 4 ·No. 2 ·2009-00-00 ·Pages e4597

Liu W, Vives-Bauza C, Acín-Peréz- R, Yamamoto A, Tan Y, Li Y, Magrané J, Stavarache MA, Shaffer S, Chang S, Kaplitt MG, Huang XY, Beal MF, Manfredi G, Li C

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.

MeSH Terms
Humans Mitochondria/pathology Mitochondrial Proteins/metabolism Models, Biological Mutation Oxidative Phosphorylation Parkinson Disease Proteasome Endopeptidase Complex/deficiency Protein Kinases/genetics alpha-Synuclein/metabolism
Chemicals
Mitochondrial Proteins alpha-Synuclein Protein Kinases PTEN-induced putative kinase Proteasome Endopeptidase Complex
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Liu Wencheng
Department of Neurology and Neurosciences, Weill Medical College of Cornell University, New York, New York, USA.
Vives-Bauza Cristofol
Acín-Peréz- Rebeca
Yamamoto Ai
Tan Yingcai
Li Yanping
Magrané Jordi
Stavarache Mihaela A
Shaffer Sebastian
Chang Simon
Kaplitt Michael G
Huang Xin-Yun
Beal M Flint
Manfredi Giovanni
Li Chenjian
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0004597
Published
2009-00-00
Epub
2009-00-26
Pages
e4597
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC2644779
Subset
IM
Grants
NINDS NIH HHS · R01 NS050199 · United States
NINDS NIH HHS · R01 NS054773 · United States
NINDS NIH HHS · NS054773 · United States
External Links
PubMed source DOI: 10.1371/journal.pone.0004597 PMC Full Text View journal details
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