The mtDNA NARP mutation activates the actin-Nrf2 signaling of antioxidant defenses

Biochem Biophys Res Commun. 2008 Apr 11;368(3):620-4. doi: 10.1016/j.bbrc.2008.01.125. Epub 2008 Feb 6.


An efficient handling of superoxides by antioxidant defenses is a crucial issue for cells with respiratory chain deficient mitochondria. We used human cultured skin fibroblasts to delineate the mechanism controlling the expression of antioxidant defenses in the case of a severe ATPase deficiency resulting from an 8993T>G mutation in the mitochondrial ATPase6 gene. We observed the nuclear translocation of the transcription factor Nrf2 associated with thinning of the actin stress fibers. The mobilization of the Nrf2 signaling pathway could be mimicked by a chemical blockade of the ATPase with a specific inhibitor, oligomycin. Interestingly enough, Nrf2 nuclear translocation was not observed in the case of a severe cytochrome oxidase deficiency, indicating that studying the status of this signaling pathway could throw some light on the importance of the oxidative insult associated with different respiratory chain defects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Antioxidants / metabolism*
  • C-Reactive Protein / genetics
  • C-Reactive Protein / metabolism*
  • Cells, Cultured
  • DNA, Mitochondrial / genetics
  • Fibroblasts / metabolism*
  • Humans
  • Mutagenesis, Site-Directed
  • NF-E2-Related Factor 2 / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Oxidative Stress / physiology
  • Signal Transduction / physiology*
  • Superoxides / metabolism


  • Actins
  • Antioxidants
  • DNA, Mitochondrial
  • NF-E2-Related Factor 2
  • Nerve Tissue Proteins
  • neuronal pentraxin
  • Superoxides
  • C-Reactive Protein
  • Adenosine Triphosphatases