In the present study mitochondrial respiratory function of fibroblasts from a patient affected by early-onset Parkinsonism carrying the homozygous W437X nonsense mutation in the PINK1 gene has been thoroughly characterized. When compared with normal fibroblasts, the patient's fibroblast mitochondria exhibited a lower respiratory activity and a decreased respiratory control ratio with cellular ATP supply relying mainly on enhanced glycolytic production. The quantity, specific activity and subunit pattern of the oxidative phosphorylation complexes were normal. However, a significant decrease of the cellular cytochrome c content was observed and this correlated with a reduced cytochrome c oxidase in situ-activity. Measurement of ROS revealed in mitochondria of the patient's fibroblasts enhanced O2•- and H 2O2 production abrogated by inhibition of complex I. No change in the glutathione-based redox buffering was, however, observed. © 2008 Springer Science+Business Media, LLC.

Mitochondrial respiratory dysfunction in familiar Parkinsonism associated with PINK1 mutation

PICCOLI, CLAUDIA;SCRIMA, ROSELLA;CAPITANIO, NAZZARENO;
2008-01-01

Abstract

In the present study mitochondrial respiratory function of fibroblasts from a patient affected by early-onset Parkinsonism carrying the homozygous W437X nonsense mutation in the PINK1 gene has been thoroughly characterized. When compared with normal fibroblasts, the patient's fibroblast mitochondria exhibited a lower respiratory activity and a decreased respiratory control ratio with cellular ATP supply relying mainly on enhanced glycolytic production. The quantity, specific activity and subunit pattern of the oxidative phosphorylation complexes were normal. However, a significant decrease of the cellular cytochrome c content was observed and this correlated with a reduced cytochrome c oxidase in situ-activity. Measurement of ROS revealed in mitochondria of the patient's fibroblasts enhanced O2•- and H 2O2 production abrogated by inhibition of complex I. No change in the glutathione-based redox buffering was, however, observed. © 2008 Springer Science+Business Media, LLC.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11369/344171
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