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mTERF2 regulates oxidative phosphorylation by modulating mtDNA transcription.

Regulation of mitochondrial protein expression is crucial for the function of the oxidative phosphorylation (OXPHOS) system. Although the basal machinery for mitochondrial transcription is known, the regulatory mechanisms are not completely understood. Here, we characterized mTERF2, a mitochondria-localized homolog of the mitochondrial transcription termination factor mTERF1. We show that inactivation of mTERF2 in the mouse results in a myopathy and memory deficits associated with decreased levels of mitochondrial transcripts and imbalanced tRNA pool. These aberrations were associated with decreased steady-state levels of OXPHOS proteins causing a decrease in respiratory function. mTERF2 binds to the mtDNA promoter region, suggesting that it affects transcription initiation. In vitro interaction studies suggest that mtDNA mediates interactions between mTERF2 and mTERF3. Our results indicate that mTERF1, mTERF2, and mTERF3 regulate transcription by acting in the same site in the mtDNA promoter region and thereby mediate fine-tuning of mitochondrial transcription and hence OXPHOS function.

Pubmed ID: 19490905

Authors

  • Wenz T
  • Luca C
  • Torraco A
  • Moraes CT

Journal

Cell metabolism

Publication Data

June 3, 2009

Associated Grants

  • Agency: NCI NIH HHS, Id: CA85700
  • Agency: NEI NIH HHS, Id: EY10804
  • Agency: NINDS NIH HHS, Id: NS041777
  • Agency: NIA NIH HHS, Id: R01 AG036871
  • Agency: NCI NIH HHS, Id: R01 CA085700
  • Agency: NCI NIH HHS, Id: R01 CA085700-07
  • Agency: NCI NIH HHS, Id: R01 CA085700-08
  • Agency: NEI NIH HHS, Id: R01 EY010804
  • Agency: NEI NIH HHS, Id: R01 EY010804-13
  • Agency: NEI NIH HHS, Id: R01 EY010804-14A1
  • Agency: NINDS NIH HHS, Id: R01 NS041777
  • Agency: NINDS NIH HHS, Id: R01 NS041777-07
  • Agency: NINDS NIH HHS, Id: R01 NS041777-08

Mesh Terms

  • Animals
  • DNA, Mitochondrial
  • Dietary Fats
  • Humans
  • Mice
  • Mice, Knockout
  • Mitochondrial Proteins
  • Oxidative Phosphorylation
  • Promoter Regions, Genetic
  • Protein Isoforms
  • Transcription Factors
  • Transcription, Genetic