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Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1.

Mitochondrial number and function are altered in response to external stimuli in eukaryotes. While several transcription/replication factors directly regulate mitochondrial genes, the coordination of these factors into a program responsive to the environment is not understood. We show here that PGC-1, a cold-inducible coactivator of nuclear receptors, stimulates mitochondrial biogenesis and respiration in muscle cells through an induction of uncoupling protein 2 (UCP-2) and through regulation of the nuclear respiratory factors (NRFs). PGC-1 stimulates a powerful induction of NRF-1 and NRF-2 gene expression; in addition, PGC-1 binds to and coactivates the transcriptional function of NRF-1 on the promoter for mitochondrial transcription factor A (mtTFA), a direct regulator of mitochondrial DNA replication/transcription. These data elucidate a pathway that directly links external physiological stimuli to the regulation of mitochondrial biogenesis and function.

Pubmed ID: 10412986


  • Wu Z
  • Puigserver P
  • Andersson U
  • Zhang C
  • Adelmant G
  • Mootha V
  • Troy A
  • Cinti S
  • Lowell B
  • Scarpulla RC
  • Spiegelman BM



Publication Data

July 9, 1999

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK54477
  • Agency: NIGMS NIH HHS, Id: GM32525

Mesh Terms

  • 3T3 Cells
  • Animals
  • Cell Line
  • DNA-Binding Proteins
  • GA-Binding Protein Transcription Factor
  • Gene Expression Regulation
  • Heat-Shock Proteins
  • Ion Channels
  • Membrane Transport Proteins
  • Mice
  • Mitochondria, Muscle
  • Mitochondrial Proteins
  • Models, Biological
  • NF-E2-Related Factor 1
  • Nuclear Respiratory Factor 1
  • Nuclear Respiratory Factors
  • Oxygen Consumption
  • Protein Biosynthesis
  • Proteins
  • Recombinant Fusion Proteins
  • Trans-Activators
  • Transcription Factors
  • Transcription, Genetic
  • Transcriptional Activation
  • Transfection