Metabolic control through the PGC-1 family of transcription coactivators.

By Jiandie D. Lin, Christoph Handschin, B. Spiegelman. Cell Metabolism, 2005

2,189 citations recorded by the source corpus.

Many complex biological programs are controlled at the level of gene transcription by DNA binding transcription factors. Recent studies have revealed a novel mode of regulation by coactivator proteins, best illustrated by the PGC-1 family of coactivators. These factors are highly responsive to a variety of environmental cues, from temperature to nutritional status to physical activity, and they coordinately regulate metabolic pathways and biological processes in a tissue-specific manner. Notably, the PGC-1 coactivators play a critical role in the maintenance of glucose, lipid, and energy homeostasis and are likely involved in the pathogenic conditions such as obesity, diabetes, neurodegeneration, and cardiomyopathy. These actions also raise new opportunities for the development of novel therapeutics.

Subfields: Biochemistry, Cell Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/c9fca8930aac1ec2ddc1c97386badcd5abbb0fac

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Citations in the corpus

The role of exercise and PGC1α in inflammation and chronic disease (2008, background): “From these studies, it is clear that PGC1α is a key mediator of many of the known beneficial effects of physical activity on skeletal muscle physiolog”
AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function. (2011, background): “…the transcriptional coactivator PGC-1a, which promotes transcription induced by several factors involved in expression of mitochondrial genes, including PPAR-a and PPAR-d, which switch on genes required for fatty acid oxidation, and nuclear respiratory factors-1 and -2 (NRF-1/-2) (Lin et al. 2005).”
Regulation of energy metabolism by long-chain fatty acids. (2014, background): “4, PGC1a acts as a coactivator of key transcription factors that mediate adaptation of skeletal muscle to endurance exercise such as PPARd, NRF, ERRa and MEF2.”
Transcriptional control of adipocyte formation. (2006, background): “During development, PGC-1a and b regulate brown adipose formation by coactivating transcription factors including nuclear respiratory factor 1 (NRF-1) and PPARg that regulate thermogenesis and mitochondrial biogenesis (Lin et al., 2005; Uldry et al., 2006).”
PARIS (ZNF746) Repression of PGC-1α Contributes to Neurodegeneration in Parkinson’s Disease (2011, neutral): “Identification of NRF-1 as a Potential In Vivo PGC-1a Target Gene in PD PGC-1a is a transcriptional coactivator that regulates a variety of genes (Lin et al., 2005; St-Pierre et al., 2006).”
CENTRAL AND PERIPHERAL CIRCADIAN CLOCKS IN MAMMALS (2012, background): “PGC-1α is critical for adaptive responses to nutritional and metabolic state, particularly following fasting (reviewed in Lin et al. 2005).”
Butyrate Improves Insulin Sensitivity and Increases Energy Expenditure in Mice (2009, background): “PGC-1 controls energy metabolism by interaction with several transcription factors, e.g., estrogen-related receptor-, nuclear respiratory factor-1 and -2, PPAR- and -, and thyroid hormone receptor, that direct gene transcription for mitochondrial biogenesis and respiration ( 8 ).”
Oncogenic BRAF regulates oxidative metabolism via PGC1α and MITF (2013, positive): “PGC1b shares significant sequence homology and functional overlap with PGC1a, including the activation of mitochondrial biogenesis and oxidative phosphorylation, but also has several distinct functions in different tissues (Lin et al., 2005b; Uldry et al., 2006; Wolfrum and Stoffel, 2006).”
mTOR controls mitochondrial oxidative function through a YY1–PGC-1α transcriptional complex (2007, methodology): “TSC2 murine embryonic fibroblasts were either (1) treated with vehicle or 20 nM rapamycin for 14 h or (2) infected with adenovirus expressing GFP or PGC-1a for 24 h.”
AMPK - a nutrient and energy sensor that maintains energy homeostasis (2012, positive): “The 'master regulator' of mitochondrial biogenesis is peroxisome proliferator-activated receptor-γ co-activator 1α (PGC1α), a co-activator that enhances the activity of several transcription factors acting on nuclear-encoded mitochondrial gene”
Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation. (2006, methodology): “The PGC-1 transcriptional coactivators appear to be major regulators of many aspects of mitochondrial biology (Lin et al., 2005a).”