| Project/Area Number |
17K19508
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biomedical structure and function and related fields
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 精子 / 乳酸脱水素酵素 / 精子形成 / 代謝物 / 酵素 |
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| Outline of Final Research Achievements |
Metabolites are sensitive indicators of moment-to-moment cellular status and activity. Expecting that tissue-specific metabolic signatures unveil a unique function of the tissue, we examined metabolomes of mouse liver and testis and found that an unusual metabolite, 2-hydroxyglutarate (2-HG), was abundantly accumulated in the testis. We clarified that lactate dehydrogenase C (LDHC), a testis-specific lactate dehydrogenase, is responsible for L-2-HG accumulation by generating and analyzing Ldhc-deficient mice. LDHA protein level was remarkably decreased in Ldhc-deficient sperm, indicating that LDHC is required for LDHA expression in the sperm. This unique functional interaction between LDH family members supports lactate dehydrogenase activity in the sperm. The severely impaired motility of Ldhc-deficient sperm suggests a substantial contribution of glycolysis to energy production for sperm motility.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、精子の受精能における乳酸脱水素酵素の重要性を明らかにした。また、乳酸脱水素酵素のアイソフォームの間での相互作用が、それらの機能をささえているという新しい知見を提供するものである。マウスの精巣において産生される2HGの重要性を明確に示すことはできなかったが、精子形成や次世代の発生になんらかの影響がでている可能性は残されている。
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