ArticleThe Journal of biological chemistry2013
Synthesis of mitochondrial DNA precursors during myogenesis, an analysis in purified C2C12 myotubes.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Epigallocatechin gallate inhibits rabies virus glycoprotein‑mediated infection in vitro.Archives of virology · 2026Article
- High-concentration MEHP triggers mtDNA depletion in undifferentiated HepaRG and C2C12 cultures and disrupts mitochondrial homeostasis in both HepaRG culture states.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Macrophage anti-bacterial activity is controlled by adenylate kinase 4-mediated mitochondrial DNA synthesis.The Journal of experimental medicine · 2026Article
- Source-Specific Photobiomodulation Regulates Mitochondrial Bioenergetics, Redox Signaling, and Functional Outputs in C2C12 Myoblasts Across Replicative Aging.International journal of molecular sciences · 2026Article
- Blockade ofmBio · 2025Article
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- Single-nucleoid architecture reveals heterogeneous packaging of mitochondrial DNA.Nature structural & molecular biology · 2024Article
- Developing a ceRNA-based lncRNA-miRNA-mRNA regulatory network to uncover roles in skeletal muscle development.Frontiers in bioinformatics · 2024Article
- SARS-CoV-2 infection induces DNA damage, through CHK1 degradation and impaired 53BP1 recruitment, and cellular senescence.Nature cell biology · 2023Article
- SMN promotes mitochondrial metabolic maturation during myogenesis by regulating the MYOD-miRNA axis.Life science alliance · 2023Article
- Ribonucleotide reductase M2B in the myofibers modulates stem cell fate in skeletal muscle.NPJ Regenerative medicine · 2022Article
- Identification of Robust and Key Differentially Expressed Genes during C2C12 Cell Myogenesis Based on Multiomics Data.International journal of molecular sciences · 2022Article
- Pyruvate Kinase M2 Supports Muscle Progenitor Cell Proliferation but Is Dispensable for Skeletal Muscle Regeneration after Injury.The Journal of nutrition · 2021Article
- Article
- Differential Effects of Rapamycin and Metformin in Combination With Rapamycin on Mechanisms of Proteostasis in Cultured Skeletal Myotubes.The journals of gerontology. Series A, Biological sciences and medical sciences · 2020Article
- LPAAT3 incorporates docosahexaenoic acid into skeletal muscle cell membranes and is upregulated by PPARδ activation.Journal of lipid research · 2018Article
- Quantitative solid-phase assay to measure deoxynucleoside triphosphate pools.Biology methods & protocols · 2018Article
- A defective dNTP pool hinders DNA replication in cell cycle-reactivated terminally differentiated muscle cells.Cell death and differentiation · 2017Article
- Oxidative DNA damage stalls the human mitochondrial replisome.Scientific reports · 2016Article
- The Deoxynucleoside Triphosphate Triphosphohydrolase Activity of SAMHD1 Protein Contributes to the Mitochondrial DNA Depletion Associated with Genetic Deficiency of Deoxyguanosine Kinase.The Journal of biological chemistry · 2015Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
During myogenesis, myoblasts fuse into multinucleated myotubes that acquire the contractile fibrils and accessory structures typical of striated skeletal muscle fibers. To support the high energy requirements of muscle contraction, myogenesis entails an increase in mitochondrial (mt) mass with stimulation of mtDNA synthesis and consumption of DNA precursors (dNTPs). Myotubes are quiescent cells and as such down-regulate dNTP production despite a high demand for dNTPs. Although myogenesis has been studied extensively, changes in dNTP metabolism have not been examined specifically. In differentiating cultures of C2C12 myoblasts and purified myotubes, we analyzed expression and activities of enzymes of dNTP biosynthesis, dNTP pools, and the expansion of mtDNA. Myotubes exibited pronounced post-mitotic modifications of dNTP synthesis with a particularly marked down-regulation of de novo thymidylate synthesis. Expression profiling revealed the same pattern of enzyme down-regulation in adult murine muscles. The mtDNA increased steadily after myoblast fusion, turning over rapidly, as revealed after treatment with ethidium bromide. We individually down-regulated p53R2 ribonucleotide reductase, thymidine kinase 2, and deoxyguanosine kinase by siRNA transfection to examine how a further reduction of these synthetic enzymes impacted myotube development. Silencing of p53R2 had little effect, but silencing of either mt kinase caused 50% mtDNA depletion and an unexpected decrease of all four dNTP pools independently of the kinase specificity. We suggest that during development of myotubes the shortage of even a single dNTP may affect all four pools through dysregulation of ribonucleotide reduction and/or dissipation of the non-limiting dNTPs during unproductive elongation of new DNA chains.
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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.