Matrilineal inheritance of complex I dysfunction in a multigenerational Parkinson's disease family

Ann Neurol. 1998 Dec;44(6):873-81. doi: 10.1002/ana.410440605.


Recent data suggesting complex I dysfunction in Parkinson's disease (PD) arises from mitochondrial DNA (mtDNA) mutation does not conclusively answer whether the responsible genetic lesion is inherited (primary) or somatic (secondary). To address this question, we identified a family in which multiple members over three generations are affected with PD through exclusively maternal lines. Cytoplasmic hybrids (cybrids) were created for 15 family members over two generations by transferring each individual's mtDNA to mtDNA-depleted human neuroblastoma cells. Eight of the 15 cybrid lines contained mtDNA obtained from maternally descended family members and seven contained mtDNA from paternally descended family members. After 6 weeks of culture, cybrid cell lines were assayed for complex I activity and oxidative stress, and mitochondrial morphology was analyzed by electron microscopy. Compared with the cybrid lines containing mtDNA from paternal descendants, cybrid lines containing mtDNA from maternal descendants had lower complex I activity, increased reactive oxygen species production, increased radical scavenging enzyme activities, and more abnormal mitochondrial morphologic features. These findings were present in cybrid lines containing mtDNA from maternal descendants with PD as well as in currently asymptomatic young maternal descendants, and support a precedent for inherited mtDNA mutation in some persons with PD.

Publication types

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

MeSH terms

  • Adult
  • DNA, Mitochondrial / genetics
  • Female
  • Free Radical Scavengers / metabolism
  • Humans
  • Hybrid Cells
  • Male
  • Microscopy, Electron
  • Middle Aged
  • Mitochondria / ultrastructure
  • Mutation / genetics
  • NAD(P)H Dehydrogenase (Quinone) / genetics*
  • NAD(P)H Dehydrogenase (Quinone) / metabolism*
  • Oxidative Stress / physiology
  • Parkinson Disease / enzymology*
  • Parkinson Disease / genetics*
  • Parkinson Disease / pathology
  • Pedigree
  • Reactive Oxygen Species / metabolism
  • Tumor Cells, Cultured


  • DNA, Mitochondrial
  • Free Radical Scavengers
  • Reactive Oxygen Species
  • NAD(P)H Dehydrogenase (Quinone)