ArticleNature communications2025
The transcriptional repressor HEY2 regulates mitochondrial oxidative respiration to maintain cardiac homeostasis.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- SYVN1-mediated succinate accumulation exacerbates heart failure.Science China. Life sciences · 2026Article
- Maternal exercise is associated with enhanced systolic reserve and altered mitochondrial respiration in adult female offspring.American journal of physiology. Heart and circulatory physiology · 2026Article
- The impactful role of the HDACs in the regulation of gene expression and as targets for disease therapy.Science advances · 2026Review
- Metabolic inflexibility across heart failure phenotypes: mechanisms and type-specific therapeutic implications.Apoptosis : an international journal on programmed cell death · 2026Review
- Multi-omics profiling of the diabetic human heart reveals coupled dysregulation in lipid metabolism, mitophagy, and extracellular matrix remodeling.Genome medicine · 2026Article
- 20(S)-protopanaxatriol ameliorates cardiac hypertrophy by activating the AMPK/PGC-1α/PPARγ signaling pathway.Journal of ginseng research · 2026Article
- Regulation of mitochondrial biogenesis and energy metabolism in the heart.Chinese medical journal · 2026Review
- Targeting the AMPK Pathway with Natural Products for Heart Failure: A Systematic Review of Preclinical Evidence.Biomedicines · 2026Review
- STEAP3 regulates ferroptosis through mitochondrial metabolic dysfunction to impact the malignant proliferation of ovarian cancer cells.Functional & integrative genomics · 2026Article
- Lactate derived from macrophages drives skin dermal fibroblasts phenotypic remodeling via MCT1-primed histone H3 lysine 23 lactylation in hypertrophic scar.Nature communications · 2026Article
- The mechanisms and therapeutic advances of interactions between breast cancer and cardiovascular diseases.Frontiers in pharmacology · 2026Review
- Cardiac involvement in Wilson disease: pathophysiology, clinical spectrum, and multimodality imaging assessment.Frontiers in cardiovascular medicine · 2026Review
- Metabolic Adaptation to Following Temperature Acclimation in Fish on the Yun-Gui Plateau.Biology · 2025Article
- Segatella exacerbates chronic heart failure via TLR4/NF-κB pathway and therapeutic potential of low-carbohydrate diet.Cell death discovery · 2025Article
- Mitochondrial Transport Proteins in Cardiovascular Diseases: Metabolic Gatekeepers, Pathogenic Mediators and Therapeutic Targets.International journal of molecular sciences · 2025Review
- Sirt4 Deficiency Promotes Cardiomyocyte Proliferation and Cardiac Repair.Journal of cellular and molecular medicine · 2025Article
- Mitochondrial homeostasis restoring peptide-drug conjugates with ROS-responsive NO releasing ability for targeted therapy of myocardial infarction.Journal of nanobiotechnology · 2025Article
- Mongolian medicine Eerdun-Wurile promotes myocardial regeneration by regulating MVDA in zebrafish.Cell regeneration (London, England) · 2025Article
- Identification of Metabolism-Related Hub Genes in Heart Failure via Comprehensive Transcriptome Analysis.Genes · 2025Article
- Ferroptosis: The Pivotal Link in Cardiovascular Diseases Pathogenesis and Therapy.International journal of general medicine · 2025Review
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21 authors.
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Abstract
Energy deprivation and metabolic rewiring of cardiomyocytes are widely recognized hallmarks of heart failure. Here, we report that HEY2 (a Hairy/Enhancer-of-split-related transcriptional repressor) is upregulated in hearts of patients with dilated cardiomyopathy. Induced Hey2 expression in zebrafish hearts or mammalian cardiomyocytes impairs mitochondrial respiration, accompanied by elevated ROS, resulting in cardiomyocyte apoptosis and heart failure. Conversely, Hey2 depletion in adult mouse hearts and zebrafish enhances the expression of mitochondrial oxidation genes and cardiac function. Multifaceted genome-wide analyses reveal that HEY2 enriches at the promoters of genes known to regulate metabolism (including Ppargc1, Esrra and Cpt1) and colocalizes with HDAC1 to effectuate histone deacetylation and transcriptional repression. Consequently, restoration of PPARGC1A/ESRRA in Hey2- overexpressing zebrafish hearts or human cardiomyocyte-like cells rescues deficits in mitochondrial bioenergetics. Knockdown of Hey2 in adult mouse hearts protects against doxorubicin-induced cardiac dysfunction. These studies reveal an evolutionarily conserved HEY2/HDAC1-Ppargc1/Cpt transcriptional module that controls energy metabolism to preserve cardiac function.
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