期刊
JOURNAL OF BIOCHEMISTRY
卷 165, 期 4, 页码 323-334出版社
OXFORD UNIV PRESS
DOI: 10.1093/jb/mvy108
关键词
2-hydroxyglutarate (2-HG); lactate dehydrogenase A (LDHA); lactate dehydrogenase C (LDHC); metabolism; sperm motility
资金
- JSPS KAKENHI [18H04794, 18H02621, 17F17116, 17K19508]
- Naito Foundation
- Research Grant of the Princess Takamatsu Cancer Research Fund [15-24728]
- Uehara Memorial Foundation
- Project for Elucidating and Controlling Mechanisms of Aging and Longevity from the AMED [18gm5010002h0001]
- Grants-in-Aid for Scientific Research [17K19508, 18H04794, 17F17116] Funding Source: KAKEN
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. 2-HG can exist as D- or L-enantiomer, and both enantiomers interfere with the activities of 2-oxoglutarate (2-OG)-dependent dioxygenases, such as the Jumonji family of histone demethylases. Whereas D-2-HG is produced by oncogenic mutants of isocitrate dehydrogenases (IDH) and known as an oncometabolite, L-2-HG was the major enantiomer detected in the testis, suggesting that a distinct mechanism underlies the testicular production of this metabolite. We clarified that lactate dehydrogenase C (LDHC), a testis-specific lactate dehydrogenase, is responsible for L-2-HG accumulation by generating and analysing Ldhc-deficient mice. Although the inhibitory effects of 2-HG on 2-OG-dependent dioxygenases were barely observed in the testis, the 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据