Mitochondrial association of alpha-synuclein causes oxidative stress

Cell Mol Life Sci. 2008 Apr;65(7-8):1272-84. doi: 10.1007/s00018-008-7589-1.


Alpha-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 alpha-synuclein with mitochondria and consequences of such interaction. Using SHSY cells overexpressing alpha-synuclein A53T mutant or wild-type, as well as isolated rat brain mitochondria, the present study shows that alpha-synuclein localizes at the mitochondrial membrane. In both SHSY cells and isolated mitochondria, interaction of alpha-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 alpha-synuclein.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cell Line, Tumor
  • Cytochromes c / metabolism
  • Humans
  • Mitochondria / enzymology
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure
  • Mutant Proteins / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / metabolism
  • Oxidative Stress*
  • Protein Binding
  • Protein Structure, Quaternary
  • Protein Transport
  • Rats
  • alpha-Synuclein / chemistry
  • alpha-Synuclein / metabolism*


  • Mutant Proteins
  • alpha-Synuclein
  • Nitric Oxide
  • Cytochromes c
  • Nitric Oxide Synthase
  • Calcium