ArticleNature metabolism2020
Mitochondrial Substrate Utilization Regulates Cardiomyocyte Cell Cycle Progression.
Article in Nature metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 179 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
179 citing papers in PubMed, 230 citations in OpenAlex.
- Bidirectional metabolic-vascular feedback loops in heart failure: From myocardial energetics to multisystem cardiometabolic crosstalk.iScience · 2026Review
- Dual-Target Cardiac Regeneration: ControllableCirculation · 2026Article
- A metabolic-epigenetic switch governs multicellular cardiac repair following succinate dehydrogenase inhibition.Nature cardiovascular research · 2026Article
- Multi-omics analysis of early reperfused ischemic heart reveals ERRβ/γ activation protects against acute myocardial infarction injury.Journal of advanced research · 2026Article
- Loss of the mitochondrial SAM transporter reveals a lipoylation-dependent metabolic vulnerability in the postnatal heart.Science advances · 2026Article
- Activation of Glucose-6-Phosphate Dehydrogenase Promotes Cardiomyocyte Cell Cycle.Circulation · 2026Article
- Small-molecule cocktail 2SM promotes heart regeneration via inducing embryonic-like cardiomyocyte state.Cell regeneration (London, England) · 2026Article
- Cardiac immunity and heart repair: Mechanism, challenge, and future direction.Chinese medical journal · 2026Review
- Signaling pathways regulating cardiac regeneration.Cell regeneration (London, England) · 2026Review
- Epigenetic Control of Mammalian Cardiomyocyte Proliferation.Current cardiology reports · 2026Review
- Cardiac regeneration and repair: the emerging mechanisms and therapeutic approaches.Molecular biomedicine · 2026Review
- Article
- CRISPR-Cas-based activation of PPARGC1A boosts endogenous mitochondria and enhances cardiac function after myocardial infarction.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Exercise Metabolic Memory Halts Pathological Cardiac Hypertrophy via PDK4.Circulation research · 2026Article
- Pro-regenerative fingerprints identified in a sub-population of adult mouse cardiomyocytes by integrative single-cell proteomics.Genome biology · 2026Article
- Myocardial metabolic remodeling in human end-stage ischemic and non-ischemic cardiomyopathy.Journal of molecular and cellular cardiology · 2026Article
- LVAD Therapy Improves Metabolic and Inflammatory State in the Heart.JACC. Basic to translational science · 2026Article
- YAP Induces a Prorenewal Metabolic State in Cardiomyocytes.Circulation · 2026Article
- Study on the spatiotemporal development of skeletal muscle in embryonic Pekin ducks.Poultry science · 2026Article
- PDK4 drives abdominal aortic aneurysm by promoting smooth muscle cell metabolic reprogramming and NLRP3-mediated pyroptosis.Nature communications · 2026Article
119 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
34 authors at 7 institutions in 4 countries.
Funding
Abstract
The neonatal mammalian heart is capable of regeneration for a brief window of time after birth. However, this regenerative capacity is lost within the first week of life, which coincides with a postnatal shift from anaerobic glycolysis to mitochondrial oxidative phosphorylation, particularly towards fatty-acid utilization. Despite the energy advantage of fatty-acid beta-oxidation, cardiac mitochondria produce elevated rates of reactive oxygen species when utilizing fatty acids, which is thought to play a role in cardiomyocyte cell-cycle arrest through induction of DNA damage and activation of DNA-damage response (DDR) pathway. Here we show that inhibiting fatty-acid utilization promotes cardiomyocyte proliferation in the postnatatal heart. First, neonatal mice fed fatty-acid deficient milk showed prolongation of the postnatal cardiomyocyte proliferative window, however cell cycle arrest eventually ensued. Next, we generated a tamoxifen-inducible cardiomyocyte-specific, pyruvate dehydrogenase kinase 4 (PDK4) knockout mouse model to selectively enhance oxidation of glycolytically derived pyruvate in cardiomyocytes. Conditional PDK4 deletion resulted in an increase in pyruvate dehydrogenase activity and consequently an increase in glucose relative to fatty-acid oxidation. Loss of PDK4 also resulted in decreased cardiomyocyte size, decreased DNA damage and expression of DDR markers and an increase in cardiomyocyte proliferation. Following myocardial infarction, inducible deletion of PDK4 improved left ventricular function and decreased remodelling. Collectively, inhibition of fatty-acid utilization in cardiomyocytes promotes proliferation, and may be a viable target for cardiac regenerative therapies.
Indexed as
Identifiers
32617517PMC7331943W3007595289What 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.