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Cell. 1999 Jul 9;98(1):115-24.

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

Author information

  • 1Dana-Farber Cancer Institute, and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.

Abstract

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.

PMID:
10412986
[PubMed - indexed for MEDLINE]
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