Transport of pyruvate into mitochondria is involved in methylmercury toxicity

Jin Yong Lee, Yosuke Ishida, Tsutomu Takahashi, Akira Naganuma, Gi Wook Hwang

研究成果: Article

9 引用 (Scopus)

抜粋

We have previously demonstrated that the overexpression of enzymes involved in the production of pyruvate, enolase 2 (Eno2) and D-lactate dehydrogenase (Dld3) renders yeast highly sensitive to methylmercury and that the promotion of intracellular pyruvate synthesis may be involved in intensifying the toxicity of methylmercury. In the present study, we showed that the addition of pyruvate to culture media in non-toxic concentrations significantly enhanced the sensitivity of yeast and human neuroblastoma cells to methylmercury. The results also suggested that methylmercury promoted the transport of pyruvate into mitochondria and that the increased pyruvate concentrations in mitochondria were involved in intensifying the toxicity of methylmercury without pyruvate being converted to acetyl-CoA. Furthermore, in human neuroblastoma cells, methylmercury treatment alone decreased the mitochondrial membrane potential, and the addition of pyruvate led to a further significant decrease. In addition, treatment with N-acetylcysteine (an antioxidant) significantly alleviated the toxicity of methylmercury and significantly inhibited the intensification of methylmercury toxicity by pyruvate. Based on these data, we hypothesize that methylmercury exerts its toxicity by raising the level of pyruvate in mitochondria and that mitochondrial dysfunction and increased levels of reactive oxygen species are involved in the action of pyruvate.

元の言語English
記事番号21528
ジャーナルScientific reports
6
DOI
出版物ステータスPublished - 2016 2 22

ASJC Scopus subject areas

  • General

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    Lee, J. Y., Ishida, Y., Takahashi, T., Naganuma, A., & Hwang, G. W. (2016). Transport of pyruvate into mitochondria is involved in methylmercury toxicity. Scientific reports, 6, [21528]. https://doi.org/10.1038/srep21528