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PINK1 loss-of-function mutations affect mitochondrial complex I activity via NdufA10 ubiquinone uncoupling

(2014) SCIENCE. 344(6180). p.203-207
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Abstract
Under resting conditions, Pink1 knockout cells and cells derived from patients with PINK1 mutations display a loss of mitochondrial complex I reductive activity, causing a decrease in the mitochondrial membrane potential. Analyzing the phosphoproteome of complex I in liver and brain from Pink1(-/-) mice, we found specific loss of phosphorylation of serine-250 in complex I subunit NdufA10. Phosphorylation of serine-250 was needed for ubiquinone reduction by complex I. Phosphomimetic NdufA10 reversed Pink1 deficits in mouse knockout cells and rescued mitochondrial depolarization and synaptic transmission defects in pink(B9)-null mutant Drosophila. Complex I deficits and adenosine triphosphate synthesis were also rescued in cells derived from PINK1 patients. Thus, this evolutionary conserved pathway may contribute to the pathogenic cascade that eventually leads to Parkinson's disease in patients with PINK1 mutations.
Keywords
MUTANTS, FISSION, MACHINERY, PATHOLOGY, MITOPHAGY, DROSOPHILA, PARKIN

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Citation

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Chicago
Morais, Vanessa A, Dominik Haddad, Katleen Craessaerts, Pieter-Jan De Bock, Jef Swerts, Sven Vilain, Liesbeth Aerts, et al. 2014. “PINK1 Loss-of-function Mutations Affect Mitochondrial Complex I Activity via NdufA10 Ubiquinone Uncoupling.” Science 344 (6180): 203–207.
APA
Morais, V. A., Haddad, D., Craessaerts, K., De Bock, P.-J., Swerts, J., Vilain, S., Aerts, L., et al. (2014). PINK1 loss-of-function mutations affect mitochondrial complex I activity via NdufA10 ubiquinone uncoupling. SCIENCE, 344(6180), 203–207.
Vancouver
1.
Morais VA, Haddad D, Craessaerts K, De Bock P-J, Swerts J, Vilain S, et al. PINK1 loss-of-function mutations affect mitochondrial complex I activity via NdufA10 ubiquinone uncoupling. SCIENCE. 2014;344(6180):203–7.
MLA
Morais, Vanessa A, Dominik Haddad, Katleen Craessaerts, et al. “PINK1 Loss-of-function Mutations Affect Mitochondrial Complex I Activity via NdufA10 Ubiquinone Uncoupling.” SCIENCE 344.6180 (2014): 203–207. Print.
@article{4400275,
  abstract     = {Under resting conditions, Pink1 knockout cells and cells derived from patients with PINK1 mutations display a loss of mitochondrial complex I reductive activity, causing a decrease in the mitochondrial membrane potential. Analyzing the phosphoproteome of complex I in liver and brain from Pink1(-/-) mice, we found specific loss of phosphorylation of serine-250 in complex I subunit NdufA10. Phosphorylation of serine-250 was needed for ubiquinone reduction by complex I. Phosphomimetic NdufA10 reversed Pink1 deficits in mouse knockout cells and rescued mitochondrial depolarization and synaptic transmission defects in pink(B9)-null mutant Drosophila. Complex I deficits and adenosine triphosphate synthesis were also rescued in cells derived from PINK1 patients. Thus, this evolutionary conserved pathway may contribute to the pathogenic cascade that eventually leads to Parkinson's disease in patients with PINK1 mutations.},
  author       = {Morais, Vanessa A and Haddad, Dominik and Craessaerts, Katleen and De Bock, Pieter-Jan and Swerts, Jef and Vilain, Sven and Aerts, Liesbeth and Overbergh, Lut and Gr{\"u}newald, Anne and Seibler, Philip and Klein, Christine and Gevaert, Kris and Verstreken, Patrik and De Strooper, Bart},
  issn         = {0036-8075},
  journal      = {SCIENCE},
  language     = {eng},
  number       = {6180},
  pages        = {203--207},
  title        = {PINK1 loss-of-function mutations affect mitochondrial complex I activity via NdufA10 ubiquinone uncoupling},
  url          = {http://dx.doi.org/10.1126/science.1249161},
  volume       = {344},
  year         = {2014},
}

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