ArticleJournal of molecular and cellular cardiology2018
Heart specific knockout of Ndufs4 ameliorates ischemia reperfusion injury.
Article in Journal of molecular and cellular cardiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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
26 citing papers in PubMed, 41 citations in OpenAlex.
- Mitochondrial-Targeted SS-31 Attenuates the Doxorubicin-Induced Cardiomyoblast H9C2 Cell Senescence.Biology · 2026Article
- Ginsenoside Rb1 attenuates coronary microvascular inflammatory injury via NDUFS4-SIRT5-DUSP1-mediated mitochondrial quality control in a murine ischemia-reperfusion model.Journal of ginseng research · 2025Article
- Mitochondrial complex-1 as a therapeutic target for cardiac diseases.Molecular and cellular biochemistry · 2025Review
- Emerging interactions between mitochondria and NADTrends in endocrinology and metabolism: TEM · 2025Review
- HTK vs. HTK-N for Coronary Endothelial Protection during Hypothermic, Oxygenated Perfusion of Hearts Donated after Circulatory Death.International journal of molecular sciences · 2024Article
- Article
- SMYD1a protects the heart from ischemic injury by regulating OPA1-mediated cristae remodeling and supercomplex formation.Basic research in cardiology · 2023Article
- Catestatin Protects Against Diastolic Dysfunction by Attenuating Mitochondrial Reactive Oxygen Species Generation.Journal of the American Heart Association · 2023Article
- Mitochondrial Oxidative Stress Mediates Bradyarrhythmia in Leigh Syndrome Mitochondrial Disease Mice.Antioxidants (Basel, Switzerland) · 2023Article
- Recombinant Adenovirus siRNA Knocking Down the Ndufs4 Gene Alleviates Myocardial Apoptosis Induced by Oxidative Stress Injury.Cardiology research and practice · 2023Article
- Metabolic rescue ameliorates mitochondrial encephalo-cardiomyopathy in murine and human iPSC models of Leigh syndrome.Clinical and translational medicine · 2022Article
- Protocol for Isolation of Cardiomyocyte from Adult Mouse and Rat.Bio-protocol · 2022Article
- Leukocytes mediate disease pathogenesis in the Ndufs4(KO) mouse model of Leigh syndrome.JCI insight · 2022Article
- Asiaticoside alleviates cardiomyocyte apoptosis and oxidative stress in myocardial ischemia/reperfusion injury via activating theAnnals of translational medicine · 2022Article
- Genetically encoded biosensors for evaluating NADCell reports methods · 2021Article
- Integrated Stress Response Couples Mitochondrial Protein Translation With Oxidative Stress Control.Circulation · 2021Article
- Identification of key pathways and genes in polycystic ovary syndrome via integrated bioinformatics analysis and prediction of small therapeutic molecules.Reproductive biology and endocrinology : RB&E · 2021Article
- A new ketogenic formulation improves functional outcome and reduces tissue loss following traumatic brain injury in adult mice.Theranostics · 2021Article
- Article
- Maintaining Myocardial Glucose Utilization in Diabetic Cardiomyopathy Accelerates Mitochondrial Dysfunction.Diabetes · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
rationaleIschemic heart disease (IHD) is a leading cause of mortality. The most effective intervention for IHD is reperfusion, which ironically causes ischemia reperfusion (I/R) injury mainly due to oxidative stress-induced cardiomyocyte death. The exact mechanism and site of reactive oxygen species (ROS) generation during I/R injury remain elusive.
objectiveWe aim to test the hypothesis that Complex I-mediated forward and reverse electron flows are the major source of ROS in I/R injury of the heart. METHODS AND
resultsWe used a genetic model of mitochondrial Complex I deficiency, in which a Complex I assembling subunit, Ndufs4 was knocked out in the heart (Ndufs4H-/-). The Langendorff perfused Ndufs4H-/- hearts exhibited significantly reduced infarct size (45.3 ± 5.5% in wild type vs 20.9 ± 8.1% in Ndufs4H-/-), recovered contractile function, and maintained mitochondrial membrane potential after no flow ischemia and subsequent reperfusion. In cultured adult cardiomyocytes from Ndufs4H-/- mice, I/R mimetic treatments caused minimal cell death. Reintroducing Ndufs4 in Ndufs4H-/- cardiomyocytes abolished the protection. Mitochondrial NADH declined much slower in Ndufs4H-/- cardiomyocytes during reperfusion suggesting decreased forward electron flow. Mitochondrial flashes, a marker for mitochondrial respiration, were inhibited in Ndufs4H-/- cardiomyocytes at baseline and during I/R, which was accompanied by preserved aconitase activity suggesting lack of oxidative damage. Finally, pharmacological blockade of forward and reverse electron flow at Complex I inhibited I/R-induced cell death.
conclusionsThese results provide the first genetic evidence supporting the central role of mitochondrial Complex I in I/R injury of mouse heart. The study also suggests that both forward and reverse electron flows underlie oxidative cardiomyocyte death during reperfusion.
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.