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Mitochondrial transcription factor A induction by redox activation of nuclear respiratory factor 1.

Publication ,  Journal Article
Piantadosi, CA; Suliman, HB
Published in: J Biol Chem
January 6, 2006

The nuclear expression of mitochondrial transcription factor A (Tfam), which is required for mitochondrial DNA (mtDNA) transcription and replication, must be linked to cellular energy needs. Because respiration generates reactive oxygen species as a side-product, we tested the idea that reactive oxygen species regulate Tfam expression through phosphorylation of nuclear respiratory factor (NRF-1) and binding to the Tfam promoter. In mitochondria-rich rat hepatoma cells that overexpress NRF-1, basal and oxidant-induced increases were found in Tfam expression and mtDNA content. Specific binding of NRF-1 to Tfam promoter was demonstrated by electrophoretic mobility shift assay and chromatin immunoprecipitation. NRF-1-Tfam binding was augmented under pro-oxidant conditions. NRF-1 gene silencing produced 1:1 knockdown of Tfam expression and decreased mtDNA content. To evaluate oxidation-reduction (redox) regulation of NRF-1 in Tfam expression, blockade of upstream phosphatidylinositol 3-kinase was used to demonstrate loss of oxidant stimulation of NRF-1 phosphorylation and Tfam expression. The oxidant response was also abrogated by specific inhibition of Akt/protein kinase B. Examination of the NRF-1 amino acid sequence revealed an Akt phosphorylation consensus at which site-directed mutagenesis abolished NRF-1 phosphorylation by Akt. Finally, Akt phosphorylation and NRF-1 translocation predictably lacked oxidant regulation in a cancer line having no PTEN tumor suppressor (HCC1937 cells). This study discloses novel redox regulation of NRF-1 phosphorylation and nuclear translocation by phosphatidylinositol 3,4,5-triphosphate kinase/Akt signaling in controlling Tfam induction by an anti-oxidant pro-survival network.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

January 6, 2006

Volume

281

Issue

1

Start / End Page

324 / 333

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Transcription Factors
  • Rats
  • Proto-Oncogene Proteins c-akt
  • Promoter Regions, Genetic
  • Phosphorylation
  • Oxidation-Reduction
  • Oxidants
  • Nuclear Respiratory Factor 1
  • Molecular Sequence Data
 

Citation

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Piantadosi, C. A., & Suliman, H. B. (2006). Mitochondrial transcription factor A induction by redox activation of nuclear respiratory factor 1. J Biol Chem, 281(1), 324–333. https://doi.org/10.1074/jbc.M508805200
Piantadosi, Claude A., and Hagir B. Suliman. “Mitochondrial transcription factor A induction by redox activation of nuclear respiratory factor 1.J Biol Chem 281, no. 1 (January 6, 2006): 324–33. https://doi.org/10.1074/jbc.M508805200.
Piantadosi CA, Suliman HB. Mitochondrial transcription factor A induction by redox activation of nuclear respiratory factor 1. J Biol Chem. 2006 Jan 6;281(1):324–33.
Piantadosi, Claude A., and Hagir B. Suliman. “Mitochondrial transcription factor A induction by redox activation of nuclear respiratory factor 1.J Biol Chem, vol. 281, no. 1, Jan. 2006, pp. 324–33. Pubmed, doi:10.1074/jbc.M508805200.
Piantadosi CA, Suliman HB. Mitochondrial transcription factor A induction by redox activation of nuclear respiratory factor 1. J Biol Chem. 2006 Jan 6;281(1):324–333.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

January 6, 2006

Volume

281

Issue

1

Start / End Page

324 / 333

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Transcription Factors
  • Rats
  • Proto-Oncogene Proteins c-akt
  • Promoter Regions, Genetic
  • Phosphorylation
  • Oxidation-Reduction
  • Oxidants
  • Nuclear Respiratory Factor 1
  • Molecular Sequence Data