ArticleFree radical biology & medicine2018
Increased TFAM binding to mtDNA damage hot spots is associated with mtDNA loss in aged rat heart.
Article in Free radical biology & medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 42 citations in OpenAlex.
- Multicellular senescence programs in the aged heart.Journal of molecular and cellular cardiology plus · 2026Review
- Environmental toxicant ochratoxin A induces psoriasis based on network toxicology machine learning and molecular docking analyses.Scientific reports · 2026Article
- Deciphering the PGC-1α-TFAM Axis in Parkinson's Disease (PD) - A Mechanism Approach Targeting Therapeutics for PD.Molecular neurobiology · 2025Review
- Resveratrol enhances post-injury muscle regeneration by regulating antioxidant and mitochondrial biogenesis.Current research in food science · 2025Article
- Epigenetic Threads of Neurodegeneration: TFAM's Intricate Role in Mitochondrial Transcription.CNS & neurological disorders drug targets · 2025Review
- DNA sequence and lesion-dependent mitochondrial transcription factor A (TFAM)-DNA-binding modulates DNA repair activities and products.Nucleic acids research · 2024Article
- HOXC11-mediated regulation of mitochondrial function modulates chemoresistance in colorectal cancer.BMC cancer · 2024Article
- APE1 regulates mitochondrial DNA damage repair after experimental subarachnoid haemorrhage in vivo and in vitro.Stroke and vascular neurology · 2024Article
- Mitochondrial Quantity and Quality in Age-Related Sarcopenia.International journal of molecular sciences · 2024Review
- Article
- HEK293T Cells with TFAM Disruption by CRISPR-Cas9 as a Model for Mitochondrial Regulation.Life (Basel, Switzerland) · 2021Article
- Review
- Effects of Bergamot Polyphenols on Mitochondrial Dysfunction and Sarcoplasmic Reticulum Stress in Diabetic Cardiomyopathy.Nutrients · 2021Review
- Biomarkers of nucleic acid oxidation - A summary state-of-the-art.Redox biology · 2021Article
- The Ketogenic Diet Reduces the Harmful Effects of Stress on Gut Mitochondrial Biogenesis in a Rat Model of Irritable Bowel Syndrome.International journal of molecular sciences · 2021Article
- Omega-3 Fatty Acids Upregulate SIRT1/3, Activate PGC-1α via Deacetylation, and Induce Nrf1 Production in 5/6 Nephrectomy Rat Model.Marine drugs · 2021Article
- Review
- The Age-Sensitive Efficacy of Calorie Restriction on Mitochondrial Biogenesis and mtDNA Damage in Rat Liver.International journal of molecular sciences · 2021Article
- Article
- Mitochondrial DNA damage in calf skeletal muscle and walking performance in people with peripheral artery disease.Free radical biology & medicine · 2020Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
The well-known age-related mitochondrial dysfunction deeply affects heart because of the tissue's large dependence on mitochondrial ATP provision. Our study revealed in aged rat heart a significant 25% decrease in mtDNA relative content, a significant 29% increase in the 4.8 Kb mtDNA deletion relative content, and a significant inverse correlation between such contents as well as a significant 38% decrease in TFAM protein amount. The TFAM-binding activity to specific mtDNA regions increased at those encompassing the mtDNA replication origins, D-loop and Ori-L. The same mtDNA regions were screened for different kinds of oxidative damage, namely Single Strand Breaks (SSBs), Double Strand Breaks (DSBs), abasic sites (AP sites) and oxidized bases as 7,8-dihydro-8-oxoguanine (8oxoG). A marked increase in the relative content of mtDNA strand damage (SSBs, DSBs and AP sites) was found in the D-loop and Ori-L regions in the aged animals, unveiling for the first time in vivo an age-related, non-stochastic accumulation of oxidative lesions in these two regions that appear as hot spots of mtDNA damage. The use of Formamidopyrimidine glycosylase (Fpg) demonstrated also a significant age-related accumulation of oxidized purines particularly in the D-loop and Ori-L regions. The detected increased binding of TFAM to the mtDNA damage hot spots in aged heart suggests a link between TFAM binding to mtDNA and loss of mitochondrial genome likely through hindrance of repair processes.
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Registered trials
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