Reactive oxygen species mediate the down-regulation of mitochondrial transcripts and proteins by tumour necrosis factor-alpha in L929 cells

Biochem J. 2003 Mar 1;370(Pt 2):609-19. doi: 10.1042/BJ20021623.


In this study, we show that reactive oxygen species production induced by tumour necrosis factor alpha (TNF-alpha) in L929 cells was associated with a decrease in the steady-state mRNA levels of the mitochondrial transcript ATPase 6-8. Simultaneously, the transcript levels of two nuclear-encoded glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and phosphofructokinase, were increased. These changes were associated with decreased protein levels of the ATPase subunit a (encoded by the mitochondrial ATPase 6 gene) and cytochrome c oxidase subunit II, and increased protein levels of phosphofructokinase. Since TNF-alpha had no effect on the amount of mitochondrial DNA, the results suggested that TNF-alpha acted at the transcriptional and/or post-transcriptional level. Reactive oxygen species scavengers, such as butylated hydroxianisole and butylated hydroxytoluene, blocked the production of free radicals, prevented the down-regulation of ATPase 6-8 transcripts, preserved the protein levels of ATPase subunit a and cytochrome c oxidase subunit II, and attenuated the cytotoxic response to TNF-alpha, indicating a direct link between these two phenomena.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death / physiology
  • Cell Nucleus / metabolism
  • DNA, Mitochondrial*
  • Down-Regulation / physiology
  • Fibrosarcoma / metabolism
  • Humans
  • Mice
  • Mitochondria / metabolism
  • Mitochondrial Proteins / metabolism
  • RNA, Messenger*
  • Reactive Oxygen Species / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism*


  • DNA, Mitochondrial
  • Mitochondrial Proteins
  • RNA, Messenger
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha