2017 Fiscal Year Final Research Report
Functional analysis of mitochondrial VDAC using synthetic ubiquinone probes
| Project/Area Number |
15K07411
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Bioorganic chemistry
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
YAMAMOTO TAKENORI 徳島大学, 先端酵素学研究所, 講師 (80457324)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | ユビキノン / ミトコンドリア / VDAC / 光親和性標識 / ケミカルバイオロジー |
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| Outline of Final Research Achievements |
The role of the voltage-dependent anion channel (VDAC) as a key link between the mitochondrial matrix and cytosol has been firmly established; however, its involvement in the regulation of mitochondrial permeability transition (PT) remains highly controversial. In the present study, we investigated whether the ubiquinone molecule directly binds to VDAC in Saccharomyces cerevisiae mitochondria by photoaffinity labeling using two photoreactive ubiquinones (PUQ-1 and PUQ-2). We demonstrated that ubiquinone specifically binds to the C-terminal region Phe221-Lys234 of the VDAC, connecting the 15th and 16th β-strand sheets. PUQ-1 and PUQ-2 both significantly suppressed the Ca2+-induced mitochondrial PT (monitored by mitochondrial swelling) at the one digit μM level. The results of the present study provided, for the first time to our knowledge, direct evidence indicating that the ubiquinone molecule specifically binds to VDAC1 through its quinone-head ring.
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| Free Research Field |
生物有機化学
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