PINK1 defect causes mitochondrial dysfunction, proteasomal deficit and alpha-synuclein aggregation in cell culture models of Parkinson's disease.
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...
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2009-01-01
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doaj-852a8703ec6941798c2d544d3cb17f232020-11-24T22:25:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0142e459710.1371/journal.pone.0004597PINK1 defect causes mitochondrial dysfunction, proteasomal deficit and alpha-synuclein aggregation in cell culture models of Parkinson's disease.Wencheng LiuCristofol Vives-BauzaRebeca Acín-Peréz-Ai YamamotoYingcai TanYanping LiJordi MagranéMihaela A StavaracheSebastian ShafferSimon ChangMichael G KaplittXin-Yun HuangM Flint BealGiovanni ManfrediChenjian LiMutations 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.http://europepmc.org/articles/PMC2644779?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wencheng Liu Cristofol Vives-Bauza Rebeca Acín-Peréz- Ai Yamamoto Yingcai Tan Yanping Li Jordi Magrané Mihaela A Stavarache Sebastian Shaffer Simon Chang Michael G Kaplitt Xin-Yun Huang M Flint Beal Giovanni Manfredi Chenjian Li |
spellingShingle |
Wencheng Liu Cristofol Vives-Bauza Rebeca Acín-Peréz- Ai Yamamoto Yingcai Tan Yanping Li Jordi Magrané Mihaela A Stavarache Sebastian Shaffer Simon Chang Michael G Kaplitt Xin-Yun Huang M Flint Beal Giovanni Manfredi Chenjian Li PINK1 defect causes mitochondrial dysfunction, proteasomal deficit and alpha-synuclein aggregation in cell culture models of Parkinson's disease. PLoS ONE |
author_facet |
Wencheng Liu Cristofol Vives-Bauza Rebeca Acín-Peréz- Ai Yamamoto Yingcai Tan Yanping Li Jordi Magrané Mihaela A Stavarache Sebastian Shaffer Simon Chang Michael G Kaplitt Xin-Yun Huang M Flint Beal Giovanni Manfredi Chenjian Li |
author_sort |
Wencheng Liu |
title |
PINK1 defect causes mitochondrial dysfunction, proteasomal deficit and alpha-synuclein aggregation in cell culture models of Parkinson's disease. |
title_short |
PINK1 defect causes mitochondrial dysfunction, proteasomal deficit and alpha-synuclein aggregation in cell culture models of Parkinson's disease. |
title_full |
PINK1 defect causes mitochondrial dysfunction, proteasomal deficit and alpha-synuclein aggregation in cell culture models of Parkinson's disease. |
title_fullStr |
PINK1 defect causes mitochondrial dysfunction, proteasomal deficit and alpha-synuclein aggregation in cell culture models of Parkinson's disease. |
title_full_unstemmed |
PINK1 defect causes mitochondrial dysfunction, proteasomal deficit and alpha-synuclein aggregation in cell culture models of Parkinson's disease. |
title_sort |
pink1 defect causes mitochondrial dysfunction, proteasomal deficit and alpha-synuclein aggregation in cell culture models of parkinson's disease. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2009-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC2644779?pdf=render |
work_keys_str_mv |
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