Mitochondrial dysfunction in skin fibroblasts from a Parkinson's disease patient with an alpha-synuclein triplication

J Parkinsons Dis. 2011;1(2):175-83. doi: 10.3233/JPD-2011-11025.


Mitochondrial dysfunction has been frequently implicated in the neurodegenerative process that underlies Parkinson's disease (PD), but the basis for this impairment is not fully understood. The goal of this study was to investigate the effects of α-synuclein (α-syn) gene multiplication on mitochondrial function in human tissue. To investigate this question, human fibroblasts were taken from a patient with parkinsonism carrying a triplication in the α-syn gene. Unexpectedly, the cells showed a significant decrease in cell growth compared to matched healthy controls. With regard to mitochondrial function, α-syn triplication fibroblasts exhibited a 39% decrease in ATP production, a 40% reduction in mitochondrial membrane potential, and a 49% reduction in complex I activity. Furthermore, they proved to be more sensitive to the effects of the nigrostrial toxicant paraquat compared to controls. Finally, siRNA knockdown of α-syn resulted in a partial rescue of mitochondrial impairment and reduction of paraquat-induced cell toxicity, suggesting that α-syn plays a causative role for mitochondrial dysfunction in these patient-derived peripheral skin fibroblasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Adult
  • Cells, Cultured
  • Electron Transport Complex I / metabolism
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Herbicides / pharmacology
  • Humans
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Membrane Potential, Mitochondrial / genetics
  • Middle Aged
  • Mitochondrial Diseases / etiology*
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / pathology
  • Paraquat / pharmacology
  • Parkinson Disease* / complications
  • Parkinson Disease* / genetics
  • Parkinson Disease* / pathology
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / pharmacology
  • Skin / pathology*
  • alpha-Synuclein / genetics*


  • Herbicides
  • RNA, Messenger
  • RNA, Small Interfering
  • alpha-Synuclein
  • Adenosine Triphosphate
  • Electron Transport Complex I
  • Paraquat