Mitochondrial dysfunction in cybrid lines expressing mitochondrial genes from patients with progressive supranuclear palsy

J Neurochem. 2000 Oct;75(4):1681-4. doi: 10.1046/j.1471-4159.2000.0751681.x.


Progressive supranuclear palsy (PSP) is a neurodegenerative movement disorder of unknown etiology. We hypothesized that mitochondrial DNA (mtDNA) aberration could occur in this disease and contribute to its pathogenesis. To address this we created transmitochondrial cytoplasmic hybrid (cybrid) cell lines expressing mitochondrial genes from persons with PSP. The presence of cybrid mtDNA aberration was screened for by biochemical assay of mitochondrial gene products. Relative to a control cybrid set, complex I activity was reduced in PSP cybrid lines (p<0.005). Antioxidant enzyme activities were elevated in PSP cybrid lines. These data suggest that mtDNA aberration occurs in PSP, causes electron transport chain pathology, and can produce oxidative stress. Further study of mitochondrial dysfunction in PSP may yield insights into why neurodegeneration occurs in this disease.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Antioxidants / metabolism
  • Blood Platelets / cytology
  • Catalase / metabolism
  • Cell Fusion
  • DNA, Mitochondrial / genetics*
  • Electron Transport / genetics
  • Electron Transport Complex I
  • Electron Transport Complex IV / metabolism
  • Female
  • Glutathione Peroxidase / metabolism
  • Glutathione Reductase / metabolism
  • Humans
  • Hybrid Cells / cytology
  • Hybrid Cells / metabolism*
  • Male
  • Mitochondria / enzymology*
  • Mitochondria / genetics*
  • NADH, NADPH Oxidoreductases / metabolism
  • Oxidative Stress / genetics
  • Superoxide Dismutase / metabolism
  • Supranuclear Palsy, Progressive / diagnosis*
  • Supranuclear Palsy, Progressive / etiology
  • Supranuclear Palsy, Progressive / genetics*
  • Tumor Cells, Cultured


  • Antioxidants
  • DNA, Mitochondrial
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • NADH, NADPH Oxidoreductases
  • Glutathione Reductase
  • Electron Transport Complex IV
  • Electron Transport Complex I