ArticleAmerican journal of physiology. Heart and circulatory physiology2016
Sirt3 protects mitochondrial DNA damage and blocks the development of doxorubicin-induced cardiomyopathy in mice.
Article in American journal of physiology. Heart and circulatory physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 146 citations in OpenAlex.
- Review
- The mitochondrial protease, LonP1, is a potential cardioprotective target for attenuating doxorubicin-induced cardiomyocyte death.Journal of translational medicine · 2026Article
- Targeted Mitochondrial ECSIT Overexpression Attenuates MASH by Increasing OTUD3 Expression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- 8-Oxoguanine: A Lesion, an Epigenetic Mark, or a Molecular Signal?International journal of molecular sciences · 2025Review
- Mitochondrial dysfunction as a key player in aggravating periodontitis among diabetic patients: review of the current scope of knowledge.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Mitochondrial sirtuins, key regulators of aging.Life medicine · 2025Review
- NADTrends in molecular medicine · 2025Review
- Mitochondrial Dysfunction is a Crucial Immune Checkpoint for Neuroinflammation and Neurodegeneration: mtDAMPs in Focus.Molecular neurobiology · 2025Review
- The role and mechanism of epigenetics in anticancer drug-induced cardiotoxicity.Basic research in cardiology · 2025Review
- Atrial Cardiomyopathy-associated Arrhythmia and the Impact of Sirtuin Signaling Pathway: A Narrative Review.Current vascular pharmacology · 2025Review
- The molecular determinants regulating redox signaling in diabetic endothelial cells.Frontiers in pharmacology · 2025Review
- SIRT3/6/7: promising therapeutic targets for pulmonary fibrosis.Frontiers in cell and developmental biology · 2025Review
- Review
- Sex difference in human diseases: mechanistic insights and clinical implications.Signal transduction and targeted therapy · 2024Review
- Article
- NSAID targets SIRT3 to trigger mitochondrial dysfunction and gastric cancer cell death.iScience · 2024Article
- Nicotinamide Riboside-Driven Modulation of SIRT3/mtROS/JNK Signaling Pathways Alleviates Myocardial Ischemia-Reperfusion Injury.International journal of medical sciences · 2024Article
- Article
- Melatonin Restores Autophagic Flux by Activating the Sirt3/TFEB Signaling Pathway to Attenuate Doxorubicin-Induced Cardiomyopathy.Antioxidants (Basel, Switzerland) · 2023Article
- The Role of Histone Deacetylases in Acute Lung Injury-Friend or Foe.International journal of molecular sciences · 2023Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Doxorubicin (Doxo) is a chemotherapeutic drug widely used to treat variety of cancers. One of the most serious side effects of Doxo is its dose-dependent and delayed toxicity to the heart. Doxo is known to induce cardiac mitochondrial damage. Recently, the mitochondrial sirtuin SIRT3 has been shown to protect mitochondria from oxidative stress. Here we show that overexpression of SIRT3 protects the heart from toxicity of Doxo by preventing the drug-induced mitochondrial DNA (mtDNA) damage. Doxo treatment caused depletion of Sirt3 levels both in primary cultures of cardiomyocytes and in mouse hearts, which led to massive acetylation of mitochondrial proteins. Doxo-induced toxicity to cardiomyocytes was associated with increased reactive oxygen species (ROS) production, mitochondrial fragmentation, and cell death. Overexpression of SIRT3 helped to attenuate Doxo-induced ROS levels and cardiomyocyte death. Sirt3 knockout (Sirt3.KO) mice could not endure the full dose of Doxo treatment, developed exacerbated cardiac hypertrophy, and died during the course of treatment, whereas Sirt3 transgenic (Sirt3.tg) mice were protected against Doxo-induced cardiotoxicity. Along with Sirt3, we also observed a concomitant decrease in levels of oxoguanine-DNA glycosylase-1 (OGG1), a major DNA glycosylase that hydrolyzes oxidized-guanine (8-oxo-dG) to guanine. Depletion of OGG1 levels was associated with increased mtDNA damage. Sirt3.KO mice and Doxo-treated mice showed increased 8-oxo-dG adducts in DNA and corresponding increase in mtDNA damage, whereas, 8-oxo-dG adducts and mtDNA damage were markedly reduced in Sirt3 overexpressing transgenic mice hearts. These results thus demonstrated that Sirt3 activation protects the heart from Doxo-induced cardiotoxicity by maintaining OGG1 levels and protecting mitochondria from DNA damage.
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