Cellular and Molecular Life Sciences

, Volume 65, Issue 7–8, pp 1272–1284

Mitochondrial association of alpha-synuclein causes oxidative stress

  • M. S. Parihar
  • A. Parihar
  • M. Fujita
  • M. Hashimoto
  • P. Ghafourifar
Research Article

Abstract.

α-Synuclein is a neuron-specific protein that contributes to the pathology of Parkinson’s disease via mitochondria-related mechanisms. The present study investigated possible interaction of α-synuclein with mitochondria and consequences of such interaction. Using SHSY cells overexpressing α-synuclein A53T mutant or wild-type, as well as isolated rat brain mitochondria, the present study shows that α-synuclein localizes at the mitochondrial membrane. In both SHSY cells and isolated mitochondria, interaction of α-synuclein with mitochondria causes release of cytochrome c, increase of mitochondrial calcium and nitric oxide, and oxidative modification of mitochondrial components. These findings suggest a pivotal role for mitochondria in oxidative stress and apoptosis induced by α-synuclein.

Keywords.

Alpha synuclein mitochondria nitric oxide Parkinson’s disease mitochondrial calcium cytochrome c mitochondrial nitric oxide synthase oxidative stress 

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Copyright information

© Birkhaueser 2008

Authors and Affiliations

  • M. S. Parihar
    • 1
  • A. Parihar
    • 1
  • M. Fujita
    • 2
  • M. Hashimoto
    • 2
  • P. Ghafourifar
    • 1
  1. 1.Department of Surgery, Davis Heart and Lung Research Institute, and Institute of Mitochondrial BiologyOhio State UniversityColumbusUSA
  2. 2.Laboratory for Chemistry and MetabolismTokyo Metropolitan Institute for Neuroscience, FuchuTokyoJapan

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