Mitochondrial association of alpha-synuclein causes oxidative stress.
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.
Parihar
M S
MS
Department of Surgery, Davis Heart and Lung Research Institute, Ohio State University, 460 West 12th Avenue, Columbus, 43210 OH, USA.
Parihar
A
A
Fujita
M
M
Hashimoto
M
M
Ghafourifar
P
P
D000818:Animals; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D050505:Mutant Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D021381:Protein Transport; D051381:Rats; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism*
D050505:Mutant Proteins; D051844:alpha-Synuclein; D009569:Nitric Oxide; D045304:Cytochromes c; D019001:Nitric Oxide Synthase; D002118:Calcium