ArticleNucleic acids research2010
Ribonucleotide reductase is not limiting for mitochondrial DNA copy number in mice.
Article in Nucleic acids research, 2010. 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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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
22 citing papers in PubMed, 31 citations in OpenAlex.
- Resveratrol ameliorates mitochondrial biogenesis and reproductive outcomes in women with polycystic ovary syndrome undergoing assisted reproduction: a randomized, triple-blind, placebo-controlled clinical trial.Journal of ovarian research · 2024Trial
- Osteoblast-derived osteomodulin restrains osteoclastogenesis via ITGB8/RRM2-mediated reduction of mitochondrial respiration and mitochondrial ATP production.Experimental & molecular medicine · 2026Article
- RRM2 promotes the proliferation of chicken myoblasts, inhibits their differentiation and muscle regeneration.Poultry science · 2024Article
- Examining Sporadic Cancer Mutations Uncovers a Set of Genes Involved in Mitochondrial Maintenance.Genes · 2023Article
- p53-Dependent Mitochondrial Compensation in Heart Failure With Preserved Ejection Fraction.Journal of the American Heart Association · 2022Article
- Hyperhomocysteinemia exacerbates acute kidney injuryFrontiers in physiology · 2022Article
- Myosin dynamics during relaxation in mouse soleus muscle and modulation by 2'-deoxy-ATP.The Journal of physiology · 2020Article
- A sensitive assay for dNTPs based on long synthetic oligonucleotides, EvaGreen dye and inhibitor-resistant high-fidelity DNA polymerase.Nucleic acids research · 2020Article
- Mitochondrial spongiotic brain disease: astrocytic stress and harmful rapamycin and ketosis effect.Life science alliance · 2020Article
- Basic biochemical characterization of cytosolic enzymes in thymidine nucleotide synthesis in adult rat tissues: implications for tissue specific mitochondrial DNA depletion and deoxynucleoside-based therapy for TK2-deficiency.BMC molecular and cell biology · 2020Article
- Ginsenosides Rb1 and Rg1 Protect Primary Cultured Astrocytes against Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury via Improving Mitochondrial Function.International journal of molecular sciences · 2019Article
- DLK proteins modulate NOTCH signaling to influence a brown or white 3T3-L1 adipocyte fate.Scientific reports · 2018Article
- Astrocytes: new players in progressive myoclonus epilepsy of Lafora type.Human molecular genetics · 2018Article
- Fast and sensitive HPLC-MS/MS method for direct quantification of intracellular deoxyribonucleoside triphosphates from tissue and cells.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2017Article
- Two transgenic mouse models for β-subunit components of succinate-CoA ligase yielding pleiotropic metabolic alterations.The Biochemical journal · 2016Article
- Nucleotide salvage deficiencies, DNA damage and neurodegeneration.International journal of molecular sciences · 2015Review
- Transgenic overexpression of ribonucleotide reductase improves cardiac performance.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Article
- Increases in mitochondrial DNA content and 4977-bp deletion upon ATM/Chk2 checkpoint activation in HeLa cells.PloS one · 2012Article
- Enzyme kinetics of the mitochondrial deoxyribonucleoside salvage pathway are not sufficient to support rapid mtDNA replication.PLoS computational biology · 2011Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Ribonucleotide reductase (RNR) is the rate-limiting enzyme in deoxyribonucleoside triphosphate (dNTP) biosynthesis, with important roles in nuclear genome maintenance. RNR is also essential for maintenance of mitochondrial DNA (mtDNA) in mammals. The mechanisms regulating mtDNA copy number in mammals are only being discovered. In budding yeast, RNR overexpression resulted in increased mtDNA levels, and rescued the disease phenotypes caused by a mutant mtDNA polymerase. This raised the question of whether mtDNA copy number increase by RNR induction could be a strategy for treating diseases with mtDNA mutations. We show here that high-level overexpression of RNR subunits (Rrm1, Rrm2 and p53R2; separately or in different combinations) in mice does not result in mtDNA copy number elevation. Instead, simultaneous expression of two RNR subunits leads to imbalanced dNTP pools and progressive mtDNA depletion in the skeletal muscle, without mtDNA mutagenesis. We also show that endogenous RNR transcripts are downregulated in response to large increases of mtDNA in mice, which is indicative of nuclear-mitochondrial crosstalk with regard to mtDNA copy number. Our results establish that RNR is not limiting for mtDNA copy number in mice, and provide new evidence for the importance of balanced dNTP pools in mtDNA maintenance in postmitotic tissues.
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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.