TY - JOUR
T1 - Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1
AU - Wu, Zhidan
AU - Puigserver, Pere
AU - Andersson, Ulf
AU - Zhang, Chenyu
AU - Adelmant, Guillaume
AU - Mootha, Vamsi
AU - Troy, Amy
AU - Cinti, Saverio
AU - Lowell, Bradford
AU - Scarpulla, Richard C.
AU - Spiegelman, Bruce M.
PY - 1999/7/9
Y1 - 1999/7/9
N2 - 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.
AB - 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.
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U2 - 10.1016/S0092-8674(00)80611-X
DO - 10.1016/S0092-8674(00)80611-X
M3 - Article
C2 - 10412986
AN - SCOPUS:0033538473
VL - 98
SP - 115
EP - 124
JO - Cell
JF - Cell
SN - 0092-8674
IS - 1
ER -