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Mitochondrial association of alpha-synuclein causes oxidative stress

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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.

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Authors and Affiliations

  1. Department of Surgery, Davis Heart and Lung Research Institute, and Institute of Mitochondrial Biology, Ohio State University, 460 West 12th Avenue, Columbus, 43210, OH, USA

    M. S. Parihar, A. Parihar & P. Ghafourifar

  2. Laboratory for Chemistry and Metabolism, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo, Japan

    M. Fujita & M. Hashimoto

Authors
  1. M. S. Parihar
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  2. A. Parihar
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  3. M. Fujita
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  4. M. Hashimoto
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  5. P. Ghafourifar
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Corresponding author

Correspondence to P. Ghafourifar.

Additional information

Received 27 December 2007; received after revision 7 February 2008; accepted 8 February 2008

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Parihar, M.S., Parihar, A., Fujita, M. et al. Mitochondrial association of alpha-synuclein causes oxidative stress. Cell. Mol. Life Sci. 65, 1272–1284 (2008). https://doi.org/10.1007/s00018-008-7589-1

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  • DOI: https://doi.org/10.1007/s00018-008-7589-1

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