ArticleProceedings of the National Academy of Sciences of the United States of America2018
Histone methyltransferase Smyd1 regulates mitochondrial energetics in the heart.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- PERM1-An Emerging Transcriptional Regulator of Mitochondrial Biogenesis: A Systematic Review.Genes · 2024Pooled it
- PERM1 Gene Therapy Prevents Pressure Overload-induced Heart Failure Through a Sarcomere-Mitochondria Energetic Microdomain.Research square · 2026Article
- Transcript isoform switching during embryonic and post-hatch development of broiler breast muscle.Poultry science · 2026Article
- ThebioRxiv : the preprint server for biology · 2026Article
- Epigenetic Functions of SMYD5 and Its Role in Development, Cancer and Other Cellular Processes.International journal of molecular sciences · 2026Review
- Developmental manganese exposure, but not concurrent lead, alters social processing selectively in male mice.iScience · 2026Article
- Ablation of ACSS2 drives alteration to cardiac and hepatic proteomic landscapes in a tissue- and sex-specific manner.Journal of proteomics · 2026Article
- Regulation of mitochondrial biogenesis and energy metabolism in the heart.Chinese medical journal · 2026Review
- Galangin 3-methyl ether alleviates mouse hypertrophic cardiomyopathy via targeting HDAC2 and subsequently inactivating the PI3K-AKT signaling pathway.Acta pharmacologica Sinica · 2026Article
- The Role of Histone Methylation in Heart Failure: Epigenetic Mechanisms and Therapeutic Perspectives.Drug design, development and therapy · 2026Review
- Histone methyltransferase SMYD1: playing a crucial role in disease progression.Frontiers in molecular biosciences · 2026Review
- Epigenetic regulation of cardiac physiology and pathophysiology: biological sex matters.The journal of cardiovascular aging · 2026Article
- PERM1 Gene Delivery via AAV Prevents Heart Failure in a Mouse Model of Pressure Overload.bioRxiv : the preprint server for biology · 2025Article
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- Hsf1 is essential for proteotoxic stress response in smyd1b-deficient embryos and fish survival under heat shock.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Heart Morphogenesis Requires Smyd1b for Proper Incorporation of the Second Heart Field in Zebrafish.Genes · 2025Article
- PERM1 regulates mitochondrial energetics through O-GlcNAcylation in the heart.Journal of molecular and cellular cardiology · 2025Article
- Leveraging metabolism for better outcomes in heart failure.Cardiovascular research · 2024Review
- SMYD1 modulates the proliferation of multipotent cardiac progenitor cells derived from human pluripotent stem cells during myocardial differentiation through GSK3β/β-catenin&ERK signaling.Stem cell research & therapy · 2024Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 6 institutions in 2 countries.
Funding
Abstract
Smyd1, a muscle-specific histone methyltransferase, has established roles in skeletal and cardiac muscle development, but its role in the adult heart remains poorly understood. Our prior work demonstrated that cardiac-specific deletion of Smyd1 in adult mice (Smyd1-KO) leads to hypertrophy and heart failure. Here we show that down-regulation of mitochondrial energetics is an early event in these Smyd1-KO mice preceding the onset of structural abnormalities. This early impairment of mitochondrial energetics in Smyd1-KO mice is associated with a significant reduction in gene and protein expression of PGC-1α, PPARα, and RXRα, the master regulators of cardiac energetics. The effect of Smyd1 on PGC-1α was recapitulated in primary cultured rat ventricular myocytes, in which acute siRNA-mediated silencing of Smyd1 resulted in a greater than twofold decrease in PGC-1α expression without affecting that of PPARα or RXRα. In addition, enrichment of histone H3 lysine 4 trimethylation (a mark of gene activation) at the PGC-1α locus was markedly reduced in Smyd1-KO mice, and Smyd1-induced transcriptional activation of PGC-1α was confirmed by luciferase reporter assays. Functional confirmation of Smyd1's involvement showed an increase in mitochondrial respiration capacity induced by overexpression of Smyd1, which was abolished by siRNA-mediated PGC-1α knockdown. Conversely, overexpression of PGC-1α rescued transcript expression and mitochondrial respiration caused by silencing Smyd1 in cardiomyocytes. These findings provide functional evidence for a role of Smyd1, or any member of the Smyd family, in regulating cardiac energetics in the adult heart, which is mediated, at least in part, via modulating PGC-1α.
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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.