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

Cell | Jul 9, 1999

http://www.ncbi.nlm.nih.gov/pubmed/10412986

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 RIS Download

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

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