PMID- 10412986
OWN - NLM
STAT- MEDLINE
DCOM- 19990809
LR  - 20161124
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 98
IP  - 1
DP  - 1999 Jul 9
TI  - Mechanisms controlling mitochondrial biogenesis and respiration through the
      thermogenic coactivator PGC-1.
PG  - 115-24
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.
FAU - Wu, Z
AU  - Wu Z
AD  - Dana-Farber Cancer Institute, and Department of Cell Biology, Harvard Medical
      School, Boston, Massachusetts 02115, USA.
FAU - Puigserver, P
AU  - Puigserver P
FAU - Andersson, U
AU  - Andersson U
FAU - Zhang, C
AU  - Zhang C
FAU - Adelmant, G
AU  - Adelmant G
FAU - Mootha, V
AU  - Mootha V
FAU - Troy, A
AU  - Troy A
FAU - Cinti, S
AU  - Cinti S
FAU - Lowell, B
AU  - Lowell B
FAU - Scarpulla, R C
AU  - Scarpulla RC
FAU - Spiegelman, B M
AU  - Spiegelman BM
LA  - eng
GR  - DK54477/DK/NIDDK NIH HHS/United States
GR  - GM32525/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (GA-Binding Protein Transcription Factor)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Ion Channels)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (NF-E2-Related Factor 1)
RN  - 0 (Nrf1 protein, mouse)
RN  - 0 (Nuclear Respiratory Factor 1)
RN  - 0 (Nuclear Respiratory Factors)
RN  - 0 (Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (Ucp2 protein, mouse)
RN  - 0 (Uncoupling Protein 2)
RN  - 0 (peroxisome-proliferator-activated receptor-gamma coactivator-1)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Cell Line
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - GA-Binding Protein Transcription Factor
MH  - *Gene Expression Regulation
MH  - Heat-Shock Proteins/metabolism
MH  - Ion Channels
MH  - *Membrane Transport Proteins
MH  - Mice
MH  - Mitochondria, Muscle/*physiology/ultrastructure
MH  - *Mitochondrial Proteins
MH  - Models, Biological
MH  - NF-E2-Related Factor 1
MH  - Nuclear Respiratory Factor 1
MH  - Nuclear Respiratory Factors
MH  - *Oxygen Consumption
MH  - Protein Biosynthesis
MH  - Proteins/genetics
MH  - Recombinant Fusion Proteins/metabolism
MH  - Trans-Activators/genetics/metabolism
MH  - Transcription Factors/genetics/*metabolism
MH  - Transcription, Genetic
MH  - Transcriptional Activation
MH  - Transfection
MH  - Uncoupling Protein 2
EDAT- 1999/07/21 00:00
MHDA- 1999/07/21 00:01
CRDT- 1999/07/21 00:00
PHST- 1999/07/21 00:00 [pubmed]
PHST- 1999/07/21 00:01 [medline]
PHST- 1999/07/21 00:00 [entrez]
AID - S0092-8674(00)80611-X [pii]
AID - 10.1016/S0092-8674(00)80611-X [doi]
PST - ppublish
SO  - Cell. 1999 Jul 9;98(1):115-24. doi: 10.1016/S0092-8674(00)80611-X.