ArticlePloS one2015
Overexpression of TFAM or twinkle increases mtDNA copy number and facilitates cardioprotection associated with limited mitochondrial oxidative stress.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 155 citations in OpenAlex.
- Nuclear Stress Bodies and Mitochondrial Signal Transduction Regulate Thermotolerance in Cattle: Insights Into Molecular Mechanisms.Animal genetics · 2026Review
- Adaptation of mtDNA content to endurance training, a cross-sectional study and an endurance training intervention.European journal of applied physiology · 2026Article
- Mitochondrial transcription factor A: linking mtDNA maintenance, mitochondrial stress responses, and inflammaging.Frontiers in aging · 2026Review
- Mitochondrial dysfunction in immune cells during the perioperative period: mechanisms, emerging therapeutic strategies, and implications for multi-organ protection.Frontiers in immunology · 2026Review
- Mitochondrial DNA Dysfunction in Cardiovascular Diseases: A Novel Therapeutic Target.Antioxidants (Basel, Switzerland) · 2025Review
- Excessive HIF-1α driven by phospholipid metabolism causes septic cardiomyopathy through cytopathic hypoxia.Nature cardiovascular research · 2025Article
- Mitochondria protect against an intracellular pathogen by restricting access to folate.Science (New York, N.Y.) · 2025Article
- Association between mitochondrial DNA copy number and production traits in pigs.Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie · 2025Article
- Epigenetic Threads of Neurodegeneration: TFAM's Intricate Role in Mitochondrial Transcription.CNS & neurological disorders drug targets · 2025Review
- Metabolic reprogramming via mitochondrial delivery for enhanced maturation of chemically induced cardiomyocyte-like cells.MedComm · 2024Article
- Maternal Low-Protein Diet Leads to Mitochondrial Dysfunction and Impaired Energy Metabolism in the Skeletal Muscle of Male Rats.International journal of molecular sciences · 2024Article
- Leukocyte mitochondrial DNA copy number and cardiovascular disease: A systematic review and meta-analysis of cohort studies.iScience · 2024Article
- iMPAQT reveals that adequate mitohormesis from TFAM overexpression leads to life extension in mice.Life science alliance · 2024Article
- Illuminating mitochondrial translation through mouse models.Human molecular genetics · 2024Review
- Mitochondrial DNA release and sensing in innate immune responses.Human molecular genetics · 2024Review
- Effect of diminazene on cardiac hypertrophy through mitophagy in rat models with hyperthyroidism induced by levothyroxine.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Deferasirox Targeting Ferroptosis Synergistically Ameliorates Myocardial Ischemia Reperfusion Injury in Conjunction With Cyclosporine A.Journal of the American Heart Association · 2024Article
- Maternally Inherited Essential Hypertension May Be Associated with the Mutations in Mitochondrial tRNAPharmacogenomics and personalized medicine · 2024Article
- Two mitochondrial HMG-box proteins, Cim1 and Abf2, antagonistically regulate mtDNA copy number in Saccharomyces cerevisiae.Nucleic acids research · 2023Article
- Mitochondrial DNA copy number is associated with incident chronic kidney disease and proteinuria in the AIDS linked to the intravenous experience cohort.Scientific reports · 2023Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMitochondrial DNA (mtDNA) copy number decreases in animal and human heart failure (HF), yet its role in cardiomyocytes remains to be elucidated. Thus, we investigated the cardioprotective function of increased mtDNA copy number resulting from the overexpression of human transcription factor A of mitochondria (TFAM) or Twinkle helicase in volume overload (VO)-induced HF. METHODS AND
resultsTwo strains of transgenic (TG) mice, one overexpressing TFAM and the other overexpressing Twinkle helicase, exhibit an approximately 2-fold equivalent increase in mtDNA copy number in heart. These TG mice display similar attenuations in eccentric hypertrophy and improved cardiac function compared to wild-type (WT) mice without any deterioration of mitochondrial enzymatic activities in response to VO, which was accompanied by a reduction in matrix-metalloproteinase (MMP) activity and reactive oxygen species after 8 weeks of VO. Moreover, acute VO-induced MMP-2 and MMP-9 upregulation was also suppressed at 24 h in both TG mice. In isolated rat cardiomyocytes, mitochondrial reactive oxygen species (mitoROS) upregulated MMP-2 and MMP-9 expression, and human TFAM (hTFAM) overexpression suppressed mitoROS and their upregulation. Additionally, mitoROS were equally suppressed in H9c2 rat cardiomyoblasts that overexpress hTFAM or rat Twinkle, both of which exhibit increased mtDNA copy number. Furthermore, mitoROS and mitochondrial protein oxidation from both TG mice were suppressed compared to WT mice.
conclusionsThe overexpression of TFAM or Twinkle results in increased mtDNA copy number and facilitates cardioprotection associated with limited mitochondrial oxidative stress. Our findings suggest that increasing mtDNA copy number could be a useful therapeutic strategy to target mitoROS in HF.
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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.