ArticleProceedings of the National Academy of Sciences of the United States of America2016
E4F1 controls a transcriptional program essential for pyruvate dehydrogenase activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 45 citations in OpenAlex.
- Article
- The transcription factor E4F1 is crucial for spermatogonial differentiation and meiosis progression in mice.BMC genomics · 2026Article
- Animal models of pyruvate dehydrogenase complex deficiency: insight into mechanisms of cerebral abnormalities and tissue-specific role in metabolism.Frontiers in medicine · 2026Review
- The Pyruvate Dehydrogenase Complex: A 90-Year-Old Enigma Shaping the Future of Structural Enzymology.Advances in experimental medicine and biology · 2026Review
- Phosphorylation of PA28γ by CK2 kinase facilitates HNSCC tumor formation and progression.Nature communications · 2025Article
- Exploring the impact of cuproptosis-related genes on immune infiltration in rheumatoid arthritis.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Pyruvate dehydrogenase alleviates macrophage autophagy in Hcy-induced ApoEActa biochimica et biophysica Sinica · 2025Article
- Mitochondrial KMT9 methylates DLAT to control pyruvate dehydrogenase activity and prostate cancer growth.Nature communications · 2025Article
- E4F1 coordinates pyruvate metabolism and the activity of the elongator complex to ensure translation fidelity during brain development.Nature communications · 2025Article
- Article
- SLC25A19 drives colorectal cancer progression by regulating p53.Cancer medicine · 2024Article
- Mitochondrial Proteins as Metabolic Biomarkers and Sites for Therapeutic Intervention in Primary and Metastatic Cancers.Mini reviews in medicinal chemistry · 2024Review
- Transcription factor E4F1 as a regulator of cell life and disease progression.Science advances · 2023Review
- Transcription factor E4F1 dictates spermatogonial stem cell fate decisions by regulating mitochondrial functions and cell cycle progression.Cell & bioscience · 2023Article
- The ENCODE4 long-read RNA-seq collection reveals distinct classes of transcript structure diversity.bioRxiv : the preprint server for biology · 2023Article
- Cuproptosis-a potential target for the treatment of osteoporosis.Frontiers in endocrinology · 2023Review
- The implications and prospect of cuproptosis-related genes and copper transporters in cancer progression.Frontiers in oncology · 2023Review
- Impact of Cuproptosis-related markers on clinical status, tumor immune microenvironment and immunotherapy in colorectal cancer: A multi-omic analysis.Computational and structural biotechnology journal · 2023Article
- Systems Biology Analysis of Temporal Dynamics That Govern Endothelial Response to Cyclic Stretch.Biomolecules · 2022Review
- RALY regulate the proliferation and expression of immune/inflammatory response genes via alternative splicing of FOS.Genes and immunity · 2022Article
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Authors and funding
18 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mitochondrial pyruvate dehydrogenase (PDH) complex (PDC) acts as a central metabolic node that mediates pyruvate oxidation and fuels the tricarboxylic acid cycle to meet energy demand. Here, we reveal another level of regulation of the pyruvate oxidation pathway in mammals implicating the E4 transcription factor 1 (E4F1). E4F1 controls a set of four genes [dihydrolipoamide acetlytransferase (Dlat), dihydrolipoyl dehydrogenase (Dld), mitochondrial pyruvate carrier 1 (Mpc1), and solute carrier family 25 member 19 (Slc25a19)] involved in pyruvate oxidation and reported to be individually mutated in human metabolic syndromes. E4F1 dysfunction results in 80% decrease of PDH activity and alterations of pyruvate metabolism. Genetic inactivation of murine E4f1 in striated muscles results in viable animals that show low muscle PDH activity, severe endurance defects, and chronic lactic acidemia, recapitulating some clinical symptoms described in PDC-deficient patients. These phenotypes were attenuated by pharmacological stimulation of PDH or by a ketogenic diet, two treatments used for PDH deficiencies. Taken together, these data identify E4F1 as a master regulator of the PDC.
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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.