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The Coactivator PGC-1 Cooperates with Peroxisome Proliferator-Activated Receptor α in Transcriptional Control of Nuclear Genes Encoding Mitochondrial Fatty Acid Oxidation Enzymes
PGC-1 is identified as a coactivator of PPAR α in the transcriptional control of mitochondrial FAO capacity, separable PPARα interaction and transactivation domains within the PGC-1 molecule are defined, and it is demonstrated that certain features of the PPARβ–PGC1 interaction are distinct from that of PP ARγ-1.
PGC-1 coactivators: inducible regulators of energy metabolism in health and disease.
This Review focuses on the biologic and physiologic functions of the PGC-1 coactivators, with particular emphasis on striated muscle, liver, and other organ systems relevant to common diseases such as diabetes and heart failure.
The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus.
PPARalpha is a critical regulator of myocardial fatty acid uptake and utilization, activation of cardiac PPARalpha regulatory pathways results in a reciprocal repression of glucose uptake and usage pathways, and derangements in myocardian energy metabolism typical of the diabetic heart can become maladaptive, leading to cardiomyopathy.
Transcriptional regulatory circuits controlling mitochondrial biogenesis and function.
This review summarizes the understanding of the transcriptional regulatory mechanisms involved in the biogenesis and energy metabolic function of mitochondria in higher organisms.
Transcriptional integration of mitochondrial biogenesis
Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis.
- J. J. Lehman, P. Barger, A. Kovács, J. Saffitz, D. Medeiros, D. Kelly
- BiologyThe Journal of clinical investigation
- 1 October 2000
It is found that PGC-1 gene expression is induced in the mouse heart after birth and in response to short-term fasting, conditions known to increase cardiac mitochondrial energy production.
Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC‐1
It is suggested that increases in PGC‐1, NRF‐ 1, andNRF‐2 represent key regulatory components of the stimulation of mitochondrial biogenesis by exercise and that P GC‐1 mediates the coordinated increases in GLUT4 and mitochondria.
Restoration of insulin-sensitive glucose transporter (GLUT4) gene expression in muscle cells by the transcriptional coactivator PGC-1
- L. F. Michael, Zhidan Wu, B. Spiegelman
- BiologyProceedings of the National Academy of Sciences…
- 13 March 2001
It is shown that adenovirus-mediated expression of the transcriptional coactivator PGC-1, which is expressed in muscle in vivo but is also deficient in cultured muscle cells, causes the total restoration of GLUT4 mRNA levels to those observed in vivo.
PGC-1α Deficiency Causes Multi-System Energy Metabolic Derangements: Muscle Dysfunction, Abnormal Weight Control and Hepatic Steatosis
It is demonstrated that PGC-1α is necessary for appropriate adaptation to the metabolic and physiologic stressors of postnatal life.
Lipin 1 is an inducible amplifier of the hepatic PGC-1alpha/PPARalpha regulatory pathway.
It is demonstrated that the expression of lipin 1 is induced by peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator 1alpha (PGC-1alpha), a transcriptional coactivators controlling several key hepatic metabolic pathways.