ArticleMolecular and cellular biology2005
PGC-1alpha coactivates PDK4 gene expression via the orphan nuclear receptor ERRalpha: a mechanism for transcriptional control of muscle glucose metabolism.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 175 papers.
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Who cites it
175 citing papers in PubMed, 353 citations in OpenAlex.
- Acute low-intensity cycling with blood-flow restriction has no effect on metabolic signaling in human skeletal muscle compared to traditional exercise.European journal of applied physiology · 2017Trial
- Combined speed endurance and endurance exercise amplify the exercise-induced PGC-1α and PDK4 mRNA response in trained human muscle.Physiological reports · 2016Trial
- RNA sequencing in adult Drosophila females identifies estrogen-related receptor-dependent transcriptional changes in metabolism, DNA replication, and translation.G3 (Bethesda, Md.) · 2026Article
- RNA Sequencing in AdultbioRxiv : the preprint server for biology · 2026Article
- Deuterated polyunsaturated fatty acids alleviate in vitro skeletal muscle dysfunction induced by oxidative stress.Free radical biology & medicine · 2026Article
- Effects of AMPK/PGC-1α on gluconeogenesis in skeletal muscle of animals under overwintering starvation and its molecular mechanism: review.Animal bioscience · 2026Article
- The nonsteroidal MR antagonist finerenone reverses Western diet-induced kidney disease by regulating mitochondrial and lipid metabolism and inflammation.American journal of physiology. Renal physiology · 2025Article
- PGC-1α Regulates Exercise Intensity-Dependent Atrial Remodeling and Fibrillation in Rats.Aging and disease · 2025Article
- Sex- and endurance training-mediated cardiovascular protection through lipids during exercise.Trends in endocrinology and metabolism: TEM · 2025Review
- ERRα and HIF-1α Cooperate to Enhance Breast Cancer Aggressiveness and Chemoresistance Under Hypoxic Conditions.Cancers · 2025Article
- Whey Protein Isolate-Encapsulated Astaxanthin Nanoemulsion More Effectively Mitigates Skeletal Muscle Atrophy in Dexamethasone-Induced Mice.Nutrients · 2025Article
- Type 3 diabetes and metabolic reprogramming of brain neurons: causes and therapeutic strategies.Molecular medicine (Cambridge, Mass.) · 2025Review
- hBMSC-EVs alleviate weightlessness-induced skeletal muscle atrophy by suppressing oxidative stress and inflammation.Stem cell research & therapy · 2025Article
- Genome-scale modeling identifies dynamic metabolic vulnerabilities during the epithelial to mesenchymal transition.Communications biology · 2024Article
- Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases.Signal transduction and targeted therapy · 2024Review
- Novel Pan-ERR Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism and Mitochondrial Function.Circulation · 2024Article
- Activation of estrogen-related receptor γ by calcium and cadmium.Frontiers in endocrinology · 2024Article
- Article
- Development and pharmacological evaluation of a new chemical series of potent pan-ERR agonists, identification of SLU-PP-915.European journal of medicinal chemistry · 2023Article
- Estrogen-related Receptor Signaling in Skeletal Muscle Fitness.International journal of sports medicine · 2023Article
115 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
The transcriptional coactivator PGC-1alpha is a key regulator of energy metabolism, yet little is known about its role in control of substrate selection. We found that physiological stimuli known to induce PGC-1alpha expression in skeletal muscle coordinately upregulate the expression of pyruvate dehydrogenase kinase 4 (PDK4), a negative regulator of glucose oxidation. Forced expression of PGC-1alpha in C(2)C(12) myotubes induced PDK4 mRNA and protein expression. PGC-1alpha-mediated activation of PDK4 expression was shown to occur at the transcriptional level and was mapped to a putative nuclear receptor binding site. Gel shift assays demonstrated that the PGC-1alpha-responsive element bound the estrogen-related receptor alpha (ERRalpha), a recently identified component of the PGC-1alpha signaling pathway. In addition, PGC-1alpha was shown to activate ERRalpha expression. Chromatin immunoprecipitation assays confirmed that PGC-1alpha and ERRalpha occupied the mPDK4 promoter in C(2)C(12) myotubes. Additionally, transfection studies using ERRalpha-null primary fibroblasts demonstrated that ERRalpha is required for PGC-1alpha-mediated activation of the mPDK4 promoter. As predicted by the effects of PGC-1alpha on PDK4 gene transcription, overexpression of PGC-1alpha in C(2)C(12) myotubes decreased glucose oxidation rates. These results identify the PDK4 gene as a new PGC-1alpha/ERRalpha target and suggest a mechanism whereby PGC-1alpha exerts reciprocal inhibitory influences on glucose catabolism while increasing alternate mitochondrial oxidative pathways in skeletal muscle.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.