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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
23
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pubmed:dateCreated |
2011-6-6
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pubmed:abstractText |
The protein ?-synuclein has a central role in Parkinson disease, but the mechanism by which it contributes to neural degeneration remains unknown. We now show that the expression of ?-synuclein in mammalian cells, including neurons in vitro and in vivo, causes the fragmentation of mitochondria. The effect is specific for synuclein, with more fragmentation by ?- than ?- or ?-isoforms, and it is not accompanied by changes in the morphology of other organelles or in mitochondrial membrane potential. However, mitochondrial fragmentation is eventually followed by a decline in respiration and neuronal death. The fragmentation does not require the mitochondrial fission protein Drp1 and involves a direct interaction of synuclein with mitochondrial membranes. In vitro, synuclein fragments artificial membranes containing the mitochondrial lipid cardiolipin, and this effect is specific for the small oligomeric forms of synuclein. ?-Synuclein thus exerts a primary and direct effect on the morphology of an organelle long implicated in the pathogenesis of Parkinson disease.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1083-351X
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pubmed:author |
pubmed-author:AzarbalFarnazF,
pubmed-author:ChengYifanY,
pubmed-author:EdwardsRobert HRH,
pubmed-author:EgamiKiyoshiK,
pubmed-author:FinkbeinerStevenS,
pubmed-author:GardnerBrookeB,
pubmed-author:LevyJon MJM,
pubmed-author:MasliahEliezerE,
pubmed-author:MunishkinaLarissaL,
pubmed-author:NakamuraKenK,
pubmed-author:NemaniVenu MVM,
pubmed-author:NussbaumRobert LRL,
pubmed-author:SesakiHiromiH,
pubmed-author:SkibinskiGaiaG,
pubmed-author:WakabayashiJunkoJ,
pubmed-author:ZhangJueJ
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pubmed:issnType |
Electronic
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pubmed:day |
10
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pubmed:volume |
286
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
20710-26
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pubmed:dateRevised |
2011-10-18
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pubmed:meshHeading |
pubmed-meshheading:21489994-Animals,
pubmed-meshheading:21489994-COS Cells,
pubmed-meshheading:21489994-Cell Death,
pubmed-meshheading:21489994-Cercopithecus aethiops,
pubmed-meshheading:21489994-HeLa Cells,
pubmed-meshheading:21489994-Humans,
pubmed-meshheading:21489994-Membrane Potential, Mitochondrial,
pubmed-meshheading:21489994-Membranes, Artificial,
pubmed-meshheading:21489994-Mice,
pubmed-meshheading:21489994-Mitochondria,
pubmed-meshheading:21489994-Neurons,
pubmed-meshheading:21489994-Oxygen Consumption,
pubmed-meshheading:21489994-Parkinson Disease,
pubmed-meshheading:21489994-alpha-Synuclein
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pubmed:year |
2011
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pubmed:articleTitle |
Direct membrane association drives mitochondrial fission by the Parkinson disease-associated protein alpha-synuclein.
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pubmed:affiliation |
Department of Neurology and Physiology, University of California, San Francisco, California 94158, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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