2012 Fiscal Year Final Research Report
Involvement of a new mitochondrial protein in the central nervous system of familial and sporadic Parkinson's disease.
Project/Area Number |
23791010
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Neurology
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Research Institution | Department of Clinical Research, National Hospital Organization Tokushima National Hospital |
Principal Investigator |
MAKI Yukiko (KUROTA Yukiko) 独立行政法人国立病院機構徳島病院(臨床研究部), 研究員 (70398014)
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Project Period (FY) |
2011 – 2012
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Keywords | 神経分子病態学 / パーキンソン病 / ミトコンドリア |
Research Abstract |
Parkin is a neuroprotective protein with many functions, including maintaining mitochondrial homeostasis. Recent evidence suggests that Parkin is recruited from the cytoplasm to damaged mitochondria with low membrane potential. We found that intracellular localization of Parkin changed with cellular growth phase. Parkin was preferentially localized in the mitochondria of cultured cells in the late log phase of growth. The mitochondria with large amounts of Parkin showed preserved membrane potentials even during treatment with carbonyl cyanide m-chlorophenylhydrazone. Here we report a novel protein named Klokin 1 that transports Parkin to the mitochondria. Klokin 1 was localized to the mitochondria and enhanced mitochondrial expression of Parkin. Klokin 1 enhanced cell viability in Parkin-silenced cells. Klokin 1 expression was enhanced in the brains of Parkin-deficient mice but not in an autopsied PARK2 brain. Our findings indicate that mitochondrial Parkin prevents mitochondrial depolarization and cellular apoptosis and that Klokin 1 may compensate for Parkin deficiency.
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Research Products
(8 results)
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[Journal Article] Parkin interacts with Klokin1 for mitochondrial import and maintenance of membrane potential.2012
Author(s)
Kuroda Y, Sako W, Goto S, Sawada T, Uchida D, Izumi Y, Takahashi T, Kagawa N, Matsumoto M, Matsumoto M, Takahashi R, Kaji R, Mitsui T.
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Journal Title
Hum Mol Genet.
Volume: 21(5)
Pages: 991-1003
Peer Reviewed
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