Collapse of mitochondrial quality control mediated by PINK1 and Parkin causes Parkinson disease
| Project/Area Number |
23687018
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Functional biochemistry
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
MATSUDA Noriyuki 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 副参事研究員 (10332272)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥26,650,000 (Direct Cost: ¥20,500,000、Indirect Cost: ¥6,150,000)
Fiscal Year 2013: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Fiscal Year 2012: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Fiscal Year 2011: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
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| Keywords | PINK1 / Parkin / ミトコンドリア / パーキンソン病 / ユビキチン |
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| Research Abstract |
1) We screened for novel Parkin substrate(s) and identified mitochondrial hexokinase I (HKI) as a candidate. Following a decrease in membrane potential, Parkin ubiquitylation of HKI leads to its proteasomal degradation. Moreover, most disease-relevant mutations of Parkin hinder this event and endogenous HKI is ubiquitylated upon dissipation of mitochondrial membrane potential in genuine-Parkin expressing cells, suggesting its physiological importance. 2) The mechanism underlying the homeostatic control of PINK1 remains unknown. We revealed that PINK1 is autophosphorylated following a decrease in membrane potential and that most disease-relevant mutations hinder this event. We demonstrated that PINK1 autophosphorylation occurs at Ser228 and Ser402, residues that are structurally clustered together. We propose that autophosphorylation of Ser228 and Ser402 in PINK1 is essential for efficient mitochondrial localization of Parkin.
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] Mitochondrial hexokinase HKI is a novel substrate of the Parkin ubiquitin ligase2012
Author(s)
Okatsu, K., Iemura, S-I., Koyano, F., Go, E., Kimura, M., Natsume, T., Tanaka, K., and Matsuda, N
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Journal Title
Biochem. Biophys. Res. Commun
Volume: 428 (1)
Issue: 1
Pages: 197-202
DOI
Related Report
Peer Reviewed
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[Journal Article] Parkin mediates apparent E2-independent monoubiquitination in vitro and contains an intrinsic activity that catalyzes polyubiquitination2011
Author(s)
Chew, KCM*., Matsuda, M*., Saisho, K., Lim, GGY., Chai, C., Tan, HM., Tanaka, K., Lim, K-L.(*equally contribution)
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Journal Title
PloS ONE.
Volume: 6(5)
Issue: 5
Pages: e19720-e19720
DOI
Related Report
Peer Reviewed
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