ArticlePloS one2013
Deficiency in repair of the mitochondrial genome sensitizes proliferating myoblasts to oxidative damage.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Sarcopenia in the Aging Process: Pathophysiological Mechanisms, Clinical Implications, and Emerging Therapeutic Approaches.International journal of molecular sciences · 2025Review
- Mitochondrial exonuclease EXOG supports DNA integrity by the removal of single-stranded DNA flaps.Nucleic acids research · 2025Article
- Causality between urate levels with sarcopenia-related traits: a bi-directional Mendelian randomization study.Frontiers in endocrinology · 2023Article
- In vitro reconstitution reveals a key role of human mitochondrial EXOG in RNA primer processing.Nucleic acids research · 2022Article
- Oxidative stress induces Z-DNA-binding protein 1-dependent activation of microglia via mtDNA released from retinal pigment epithelial cells.The Journal of biological chemistry · 2022Article
- PGC-1ɑ Mediated-EXOG, a Specific Repair Enzyme for Mitochondrial DNA, Plays an Essential Role in the Rotenone-Induced Neurotoxicity of PC12 Cells.Journal of molecular neuroscience : MN · 2021Article
- A unique exonuclease ExoG cleaves between RNA and DNA in mitochondrial DNA replication.Nucleic acids research · 2019Article
- Differential regulation of cellular stress responses by the endoplasmic reticulum-resident Selenoprotein S (Seps1) in proliferating myoblasts versus myotubes.Physiological reports · 2018Article
- Targeting myomiRs by tocotrienol-rich fraction to promote myoblast differentiation.Genes & nutrition · 2018Article
- The MacroH2A1.1 - PARP1 Axis at the Intersection Between Stress Response and Metabolism.Frontiers in genetics · 2018Article
- Risky repair: DNA-protein crosslinks formed by mitochondrial base excision DNA repair enzymes acting on free radical lesions.Free radical biology & medicine · 2017Review
- A domain in human EXOG converts apoptotic endonuclease to DNA-repair exonuclease.Nature communications · 2017Article
- Tocotrienol-Rich Fraction Ameliorates Antioxidant Defense Mechanisms and Improves Replicative Senescence-Associated Oxidative Stress in Human Myoblasts.Oxidative medicine and cellular longevity · 2017Article
- Inhibition of hydrogen sulfide biosynthesis sensitizes lung adenocarcinoma to chemotherapeutic drugs by inhibiting mitochondrial DNA repair and suppressing cellular bioenergetics.Scientific reports · 2016Article
- Classical non-homologous end-joining pathway utilizes nascent RNA for error-free double-strand break repair of transcribed genes.Nature communications · 2016Article
- Ethanol Extract of Ganoderma lucidum Augments Cellular Anti-oxidant Defense through Activation of Nrf2/HO-1.Journal of pharmacopuncture · 2016Article
- AP39, a Mitochondria-Targeted Hydrogen Sulfide Donor, Supports Cellular Bioenergetics and Protects against Alzheimer's Disease by Preserving Mitochondrial Function in APP/PS1 Mice and Neurons.Oxidative medicine and cellular longevity · 2016Article
- Mitochondrial DNA damage induced autophagy, cell death, and disease.Frontiers in bioscience (Landmark edition) · 2016Review
- Article
- Opposing roles of mitochondrial and nuclear PARP1 in the regulation of mitochondrial and nuclear DNA integrity: implications for the regulation of mitochondrial function.Nucleic acids research · 2014Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Reactive oxygen species (ROS), generated as a by-product of mitochondrial oxidative phosphorylation, are particularly damaging to the genome of skeletal muscle because of their high oxygen consumption. Proliferating myoblasts play a key role during muscle regeneration by undergoing myogenic differentiation to fuse and restore damaged muscle. This process is severely impaired during aging and in muscular dystrophies. In this study, we investigated the role of oxidatively damaged DNA and its repair in the mitochondrial genome of proliferating skeletal muscle progenitor myoblasts cells and their terminally differentiated product, myotubes. Using the C2C12 cell line as a well-established model for skeletal muscle differentiation, we show that myoblasts are highly sensitive to ROS-mediated DNA damage, particularly in the mitochondrial genome, due to deficiency in 5' end processing at the DNA strand breaks. Ectopic expression of the mitochondrial-specific 5' exonuclease, EXOG, a key DNA base excision/single strand break repair (BER/SSBR) enzyme, in myoblasts but not in myotubes, improves the cell's resistance to oxidative challenge. We linked loss of myoblast viability by activation of apoptosis with deficiency in the repair of the mitochondrial genome. Moreover, the process of myoblast differentiation increases mitochondrial biogenesis and the level of total glutathione. We speculate that our data may provide a mechanistic explanation for depletion of proliferating muscle precursor cells during the development of sarcopenia, and skeletal muscle dystrophies.
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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.