Mitochondrial respiratory dysfunction in familiar parkinsonism associated with PINK1 mutation

Neurochem Res. 2008 Dec;33(12):2565-74. doi: 10.1007/s11064-008-9729-2. Epub 2008 May 13.

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 O(2)(*-) and H(2)O(2) production abrogated by inhibition of complex I. No change in the glutathione-based redox buffering was, however, observed.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Adult
  • Cells, Cultured
  • Cytochromes c / metabolism
  • Glutathione / metabolism
  • Humans
  • Immunohistochemistry
  • Microscopy, Confocal
  • Mitochondria / enzymology
  • Mitochondria / metabolism
  • Mitochondria / physiology*
  • Mutation*
  • Oxidative Phosphorylation
  • Parkinson Disease / genetics*
  • Parkinson Disease / metabolism
  • Parkinson Disease / physiopathology
  • Protein Kinases / genetics*
  • Reactive Oxygen Species / metabolism
  • Subcellular Fractions / metabolism

Substances

  • Reactive Oxygen Species
  • Adenosine Triphosphate
  • Cytochromes c
  • Protein Kinases
  • PTEN-induced putative kinase
  • Glutathione