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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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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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 / 膜透過性亢進 / クリックケミストリー |
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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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Report
(4 results)
Research Products
(47 results)
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[Journal Article] Specific methylation of Asp160 (49 kDa subunit) located inside the quinone binding cavity of bovine mitochondrial complex I2016
Author(s)
Murai, M., Inaoka, H., Masuya, T., Aburaya, S., Aoki, W., and Miyoshi, H.
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Journal Title
Biochemistry
Volume: 55
Pages: 3189-3197
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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