ArticleAntioxidants & redox signaling2014
Mitochondrial genome linearization is a causative factor for cardiomyopathy in mice and Drosophila.
Article in Antioxidants & redox signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- Mitochondrial quality control as a therapeutic target in cardiovascular disease: Mechanistic insights and future directions.Journal of translational internal medicine · 2025Article
- Mitochondria and myocardial ischemia/reperfusion injury: Effects of Chinese herbal medicine and the underlying mechanisms.Journal of pharmaceutical analysis · 2025Review
- Mitochondrial non-energetic function and embryonic cardiac development.Frontiers in cell and developmental biology · 2024Review
- Zinc Overload Induces Damage to H9c2 Cardiomyocyte Through Mitochondrial Dysfunction and ROS-Mediated Mitophagy.Cardiovascular toxicology · 2023Article
- A genome on shaky ground: exploring the impact of mitochondrial DNA integrity on Parkinson's disease by highlighting the use of cybrid models.Cellular and molecular life sciences : CMLS · 2022Review
- Mitochondrial Fusion Protein Mfn2 and Its Role in Heart Failure.Frontiers in molecular biosciences · 2021Review
- Mitochondrial quality control mechanisms as molecular targets in cardiac ischemiaActa pharmaceutica Sinica. B · 2020Review
- Mitofusins as mitochondrial anchors and tethers.Journal of molecular and cellular cardiology · 2020Review
- Mitofusin 2 Dysfunction and Disease in Mice and Men.Frontiers in physiology · 2020Review
- Assessing the effects of mitofusin 2 deficiency in the adult heart using 3D electron tomography.Physiological reports · 2017Article
- Article
- Mitochondrial pathways to cardiac recovery: TFAM.Heart failure reviews · 2016Review
- Central Parkin: The evolving role of Parkin in the heart.Biochimica et biophysica acta · 2016Review
- Mitochondrial DNA damage induced autophagy, cell death, and disease.Frontiers in bioscience (Landmark edition) · 2016Review
- Regulation of mitochondrial functions by protein phosphorylation and dephosphorylation.Cell & bioscience · 2016Review
- Mitochondrial dynamism and heart disease: changing shape and shaping change.EMBO molecular medicine · 2015Review
- Mitoconfusion: noncanonical functioning of dynamism factors in static mitochondria of the heart.Cell metabolism · 2015Review
- Mitochondrial fission and fusion factors reciprocally orchestrate mitophagic culling in mouse hearts and cultured fibroblasts.Cell metabolism · 2015Article
- Dynamic monitoring of oxidative DNA double-strand break and repair in cardiomyocytes.Cardiovascular pathology : the official journal of the Society for Cardiovascular PathologyArticle
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
aimsMitofusin (Mfn)2 redundantly promotes mitochondrial outer membrane tethering and organelle fusion with Mfn1, and uniquely functions as the mitochondrial receptor for Parkin during PTEN-induced putative kinase 1 (PINK1)-Parkin-mediated mitophagy. Selective deletion of Mfn2 with retention of Mfn1 preserves mitochondrial fusion while rendering damaged mitochondria resistant to normal quality control culling mechanisms. Consequently, neuron and cardiomyocyte-specific Mfn2 gene ablation is associated with accumulation of damaged mitochondria and organ dysfunction. Here, we determined how mitochondrial DNA (mtDNA) damage contributes to cardiomyopathy in Mfn2-deficient hearts.
resultsRNA sequencing of Mfn2-deficient hearts revealed increased expression of some nuclear-encoded mitochondrial genes, but mitochondrial-encoded transcripts were not upregulated in parallel and mtDNA content was decreased. Ultra-deep sequencing of mtDNA showed no increase in single nucleotide mutations, but copy number variations representing insertion-deletion (in-del) mutations were induced over time by cardiomyocyte-specific Mfn2 deficiency. Double-strand mtDNA breaks in the form of in-dels were confirmed by polymerase chain reaction, and in the form of linear mitochondrial genomes were identified by southern blot analysis. Linearization of Drosophila cardiomyocyte mtDNA using conditional cardiomyocyte-specific expression of mitochondrial targeted XhoI recapitulated the cardiomyopathy of Mfn2-deficient mouse hearts. INNOVATION: This is the first description of mitochondrial genome linearization as a causative factor in cardiomyopathy.
conclusionOne of the consequences of interrupting mitochondrial culling by the PINK1-Mfn2-Parkin mechanism is an increase in mtDNA double-stranded breaks, which adversely impact mitochondrial function and DNA replication.
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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.