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

Zhidan Wu, Pere Puigserver, Ulf Andersson, Chenyu Zhang, Guillaume Adelmant, Vamsi Mootha, Amy Troy, Saverio Cinti, Bradford Lowell, Richard C. Scarpulla, Bruce M. Spiegelman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2740 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)115-124
Number of pages10
JournalCell
Volume98
Issue number1
DOIs
StatePublished - Jul 9 1999

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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