Papers

Peer-reviewed International journal
4 1, 2019

Lactate dehydrogenase C is required for the protein expression of a sperm-specific isoform of lactate dehydrogenase A.

Journal of biochemistry
  • Mina Dodo
  • ,
  • Hiroshi Kitamura
  • ,
  • Hiroki Shima
  • ,
  • Daisuke Saigusa
  • ,
  • Sisca Meida Wati
  • ,
  • Nao Ota
  • ,
  • Fumiki Katsuoka
  • ,
  • Hatsune Chiba
  • ,
  • Hiroaki Okae
  • ,
  • Takahiro Arima
  • ,
  • Kazuhiko Igarashi
  • ,
  • Takeyoshi Koseki
  • ,
  • Hiroki Sekine
  • ,
  • Hozumi Motohashi

Volume
165
Number
4
First page
323
Last page
334
Language
English
Publishing type
DOI
10.1093/jb/mvy108

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.

Link information
DOI
https://doi.org/10.1093/jb/mvy108
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30590713