ArticleNature2012
Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure.
Article in Nature, 2012. 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 698 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
698 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,160 citations in OpenAlex.
- Reprogramming heart failure: physiological orchestration and mechanistic decoding of exercise benefits.BMC cardiovascular disorders · 2025Pooled it
- Myocardial Immune Cells: The Basis of Cardiac Immunology.Journal of immunology (Baltimore, Md. : 1950) · 2023Pooled it
- Remodeling of innate antiviral immunity in aging.Cell insight · 2026Review
- Admission serum mitochondrial DNA relative abundance is associated with angiographic no-reflow or slow-flow after primary percutaneous coronary intervention in STEMI.Journal of thrombosis and thrombolysis · 2026Article
- After delivery: How recipient cells shape the fate and function of transplanted mitochondria.Clinical and translational medicine · 2026Review
- Multi-omics profiling of circulating proteins and metabolites in persistent atrial fibrillation: VDAC1 identified as a candidate circulating protein.International journal of cardiology. Heart & vasculature · 2026Article
- Cardiovascular-kidney-metabolic syndrome as a mitochondrial systems disorder.Nature reviews. Nephrology · 2026Review
- Experimental workflows for the accurate identification of mitochondrial redox events.Redox biology · 2026Review
- Mitochondrial Quality Control Links Exercise to Sterile Inflammation in the Cardiovascular System: A Narrative Review.Antioxidants (Basel, Switzerland) · 2026Review
- A Systems View of Posterior Capsule Opacification: TGF-β/ROS Signaling, Mitochondrial Homeostasis, and Injury/Aging Cues-Therapeutic Opportunities.Investigative ophthalmology & visual science · 2026Review
- Mitochondrial Distress Signals at the Heart-Liver Interface: Molecular Links Between MASLD and Heart Failure.International journal of molecular sciences · 2026Review
- Article
- Maternal hyperglycemia-induced O-GlcNAcylation of CaMKIIδ promotes mtDNA release and cardiac remodeling in offspring.Nature communications · 2026Article
- Cancer immunotherapy targeting murine myeloid cells requires endosomal pattern recognition.Nature communications · 2026Article
- The mitochondrial protease, LonP1, is a potential cardioprotective target for attenuating doxorubicin-induced cardiomyocyte death.Journal of translational medicine · 2026Article
- Residual cardiovascular risk in coronary artery disease: from pathophysiology to established and novel therapies.Nature reviews. Cardiology · 2026Review
- Therapeutic Potential of Ginkgolic Acid C17:1 in Modulating PTEN/mtDNA/TLR9 Axis for Alleviating Chronic Pseudomonas Aeruginosa Infection in Bronchiectasis.Iranian journal of biotechnology · 2026Article
- Neuropsychiatric disorders in pulmonary fibrosis: from brain network alterations to inflammatory mechanisms and therapeutic implications.Journal of neuroinflammation · 2026Review
- Cellular Senescence and the SASP in HFpEF: Pathogenic Mechanisms and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Mitochondria as convergence hubs for innate immunity pathways.Communications biology · 2026Review
638 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Commented on by
- Erratum issued
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Heart failure is a leading cause of morbidity and mortality in industrialized countries. Although infection with microorganisms is not involved in the development of heart failure in most cases, inflammation has been implicated in the pathogenesis of heart failure. However, the mechanisms responsible for initiating and integrating inflammatory responses within the heart remain poorly defined. Mitochondria are evolutionary endosymbionts derived from bacteria and contain DNA similar to bacterial DNA. Mitochondria damaged by external haemodynamic stress are degraded by the autophagy/lysosome system in cardiomyocytes. Here we show that mitochondrial DNA that escapes from autophagy cell-autonomously leads to Toll-like receptor (TLR) 9-mediated inflammatory responses in cardiomyocytes and is capable of inducing myocarditis and dilated cardiomyopathy. Cardiac-specific deletion of lysosomal deoxyribonuclease (DNase) II showed no cardiac phenotypes under baseline conditions, but increased mortality and caused severe myocarditis and dilated cardiomyopathy 10 days after treatment with pressure overload. Early in the pathogenesis, DNase II-deficient hearts showed infiltration of inflammatory cells and increased messenger RNA expression of inflammatory cytokines, with accumulation of mitochondrial DNA deposits in autolysosomes in the myocardium. Administration of inhibitory oligodeoxynucleotides against TLR9, which is known to be activated by bacterial DNA, or ablation of Tlr9 attenuated the development of cardiomyopathy in DNase II-deficient mice. Furthermore, Tlr9 ablation improved pressure overload-induced cardiac dysfunction and inflammation even in mice with wild-type Dnase2a alleles. These data provide new perspectives on the mechanism of genesis of chronic inflammation in failing hearts.
Indexed as
Identifiers
What OpenQuestion holds
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.