ArticleCirculation2022
Heteroplasmy of Wild-Type Mitochondrial DNA Variants in Mice Causes Metabolic Heart Disease With Pulmonary Hypertension and Frailty.
Article in Circulation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
What it found
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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.
The trial behind it
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Paternal leakage of mitochondrial DNA is genetically controlled in Drosophila.G3 (Bethesda, Md.) · 2026Article
- Shifting the Balance: Mitochondrial Heteroplasmy as a Driver of Cardiac Disease.Circulation research · 2026Review
- Mitochondrial Dysfunction: A Critical Link Between Maternal Diet and Offspring Metabolic Health.Biomolecules · 2026Review
- Fertility clinics are offering young mitochondria in controversial fertility technique.Nature · 2026Article
- Mitochondrial Transfer to Endothelial Cells: Mechanisms, Evidence, and Therapeutic Potential.Circulation research · 2026Review
- Mitochondrial transfer and transplantation in tendon, ligament, and enthesis repair: current evidence, mechanistic rationale, and regenerative opportunities.Frontiers in cell and developmental biology · 2026Review
- Structural diversity and evolutionary constraints of oxidative phosphorylation.Cell genomics · 2025Article
- Pervasive non-random mitochondrial DNA heteroplasmy in the hybrid water frog Pelophylax esculentus.BMC ecology and evolution · 2025Article
- Mitochondrial DNA copy number associated dementia risk by somatic mutations and frailty.GeroScience · 2025Article
- Recommendations for mitochondria transfer and transplantation nomenclature and characterization.Nature metabolism · 2025Review
- Supplementation of Oocytes by Microinjection with Extra Copies of mtDNA Alters Metabolite Profiles and Interactions with Expressed Genes in a Tissue-Specific Manner.Biomolecules · 2024Article
- The multifaceted role of mitochondria in cardiac function: insights and approaches.Cell communication and signaling : CCS · 2024Review
- Understanding the Role of Oxidative Stress in Platelet Alterations and Thrombosis Risk among Frail Older Adults.Biomedicines · 2024Review
- DUSP1 protects against ischemic acute kidney injury through stabilizing mtDNA via interaction with JNK.Cell death & disease · 2023Article
- The Therapeutic Strategies Targeting Mitochondrial Metabolism in Cardiovascular Disease.Pharmaceutics · 2022Review
- Roles of Mitochondrial DNA Damage in Kidney Diseases: A New Biomarker.International journal of molecular sciences · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
18 authors at 9 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn most eukaryotic cells, the mitochondrial DNA (mtDNA) is transmitted uniparentally and present in multiple copies derived from the clonal expansion of maternally inherited mtDNA. All copies are therefore near-identical, or homoplasmic. The presence of >1 mtDNA variant in the same cytoplasm can arise naturally or result from new medical technologies aimed at preventing mitochondrial genetic diseases and improving fertility. The latter is called divergent nonpathologic mtDNA heteroplasmy (DNPH). We hypothesized that DNPH is maladaptive and usually prevented by the cell.
methodsWe engineered and characterized DNPH mice throughout their lifespan using transcriptomic, metabolomic, biochemical, physiologic, and phenotyping techniques. We focused on in vivo imaging techniques for noninvasive assessment of cardiac and pulmonary energy metabolism.
resultsWe show that DNPH impairs mitochondrial function, with profound consequences in critical tissues that cannot resolve heteroplasmy, particularly cardiac and skeletal muscle. Progressive metabolic stress in these tissues leads to severe pathology in adulthood, including pulmonary hypertension and heart failure, skeletal muscle wasting, frailty, and premature death. Symptom severity is strongly modulated by the nuclear context.
conclusionsMedical interventions that may generate DNPH should address potential incompatibilities between donor and recipient mtDNA.
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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.