Neurochemical Research

, 33:2565

Mitochondrial Respiratory Dysfunction in Familiar Parkinsonism Associated with PINK1 Mutation

Authors

  • Claudia Piccoli
    • Department of Biomedical SciencesUniversity of Foggia
  • Annamaria Sardanelli
    • Department of Medical Biochemistry, Biology and PhysicsUniversity of Bari
  • Rosella Scrima
    • Department of Biomedical SciencesUniversity of Foggia
  • Maria Ripoli
    • Department of Biomedical SciencesUniversity of Foggia
  • Giovanni Quarato
    • Department of Biomedical SciencesUniversity of Foggia
  • Annamaria D’Aprile
    • Department of Biomedical SciencesUniversity of Foggia
  • Francesco Bellomo
    • Department of Medical Biochemistry, Biology and PhysicsUniversity of Bari
  • Salvatore Scacco
    • Department of Medical Biochemistry, Biology and PhysicsUniversity of Bari
  • Giuseppe De Michele
    • Department of Neurological SciencesFederico II University
  • Alessandro Filla
    • Department of Neurological SciencesFederico II University
  • Arcangela Iuso
    • Department of Medical Biochemistry, Biology and PhysicsUniversity of Bari
  • Domenico Boffoli
    • Department of Biomedical SciencesUniversity of Foggia
  • Nazzareno Capitanio
    • Department of Biomedical SciencesUniversity of Foggia
    • Department of Medical Biochemistry, Biology and PhysicsUniversity of Bari
    • Institute of Biomembranes and BioenergeticsItalian Research Council
Original Paper

DOI: 10.1007/s11064-008-9729-2

Cite this article as:
Piccoli, C., Sardanelli, A., Scrima, R. et al. Neurochem Res (2008) 33: 2565. doi:10.1007/s11064-008-9729-2

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 H2O2 production abrogated by inhibition of complex I. No change in the glutathione-based redox buffering was, however, observed.

Keywords

Parkinson diseasePINK1MitochondriaOxidative phosphorylationReactive oxygen speciesCytochrome c

Copyright information

© Springer Science+Business Media, LLC 2008