ArticleScience (New York, N.Y.)2015
Imbalanced OPA1 processing and mitochondrial fragmentation cause heart failure in mice.
Article in Science (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06747429 (Cardiac Metabolic Reprogramming by a Nutritional Intervention), which is not on this map. Cited by 318 papers, 1 of them a synthesis 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.
Cardiac Metabolic Reprogramming by a Nutritional Intervention: the High Fat Diet for Heart Failure (HF4HF) Study, a proof-of Concept Randomized Controlled Trial
Who cites it
318 citing papers in PubMed, 1 synthesis or guideline pooled it, 535 citations in OpenAlex.
- Mitochondrial dysfunction in cardiovascular disease: Towards exercise regulation of mitochondrial function.Frontiers in physiology · 2023Pooled it
- Edited HSPCs rescue frataxin deficiency and inflammation-driven multisystemic pathology in Friedreich's ataxia mice.The Journal of clinical investigation · 2026Article
- Higher Myocardial miR-1-3p, miR-30a-5p, miR-34a-5p, and Lower miR208a-3p Levels are Associated with Lower Age at the Time of Heart Transplantation.Journal of cardiovascular translational research · 2026Article
- Mitochondrial Quality Control in Inherited Mitochondrial Cardiomyopathy: Convergent Pathobiology and a Testable Therapeutic Framework.International journal of molecular sciences · 2026Review
- OMA1 protects from liver injury and tumorigenesis during aging by controlling hepatic immunogenicity.The EMBO journal · 2026Article
- Mitochondrial quality control in health and disease: mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Mitochondrial Quality Control in Age-Related Diseases: From Molecular Architecture to Precision Therapeutics.Antioxidants (Basel, Switzerland) · 2026Review
- Mitochondrial protein OPA3 sustains cardiac function by regulating calcium handling in male mice.Nature communications · 2026Article
- A high-fat diet nutritional intervention reprograms cardiac metabolism and improves systolic function in a pig model of heart failure with reduced ejection fraction.Basic research in cardiology · 2026Article
- Stress-induced OMA1-mediated cleavage of AIFM1 suppresses cell growth by controlling mitochondrial OXPHOS activity.The EMBO journal · 2026Article
- Extracellular Vesicles Modulation by an Adiponectin Receptor Agonist Provides Cardioprotection for Myocardial Ischemic Injury.Advanced healthcare materials · 2026Article
- Ketogenic diet, cardiometabolic diseases and aging.Journal of geriatric cardiology : JGC · 2026Article
- Proteolytic control of mitochondrial protein translocases.Protein science : a publication of the Protein Society · 2026Review
- Regulation of mitochondrial biogenesis and energy metabolism in the heart.Chinese medical journal · 2026Review
- Attenuated lamin A-prohibitin2 interaction leads to mitochondrial dysfunction in LMNA 289 A>G-mediated dilated cardiomyopathy.The Journal of biological chemistry · 2026Article
- Stress adaptation of mitochondrial protein import by OMA1-mediated degradation of DNAJC15.Nature structural & molecular biology · 2026Article
- PI3K/Akt/mTOR signaling pathway mediates energy metabolic reprogramming and regulates mitochondrial homeostasis in host cells exposed toMicrobiology spectrum · 2026Article
- Mutant CHCHD10 disrupts cytochrome c oxidation and activates mitochondrial retrograde signaling.EMBO molecular medicine · 2026Article
- OPA1 Deficiency Impairs NGF Signaling and Drives Sympathetic Neurodegeneration.JACC. Basic to translational science · 2026Article
- Cystinosis and Cellular Energy Failure: Mitochondria at the Crossroads.International journal of molecular sciences · 2026Review
258 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial morphology is shaped by fusion and division of their membranes. Here, we found that adult myocardial function depends on balanced mitochondrial fusion and fission, maintained by processing of the dynamin-like guanosine triphosphatase OPA1 by the mitochondrial peptidases YME1L and OMA1. Cardiac-specific ablation of Yme1l in mice activated OMA1 and accelerated OPA1 proteolysis, which triggered mitochondrial fragmentation and altered cardiac metabolism. This caused dilated cardiomyopathy and heart failure. Cardiac function and mitochondrial morphology were rescued by Oma1 deletion, which prevented OPA1 cleavage. Feeding mice a high-fat diet or ablating Yme1l in skeletal muscle restored cardiac metabolism and preserved heart function without suppressing mitochondrial fragmentation. Thus, unprocessed OPA1 is sufficient to maintain heart function, OMA1 is a critical regulator of cardiomyocyte survival, and mitochondrial morphology and cardiac metabolism are intimately linked.
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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.