ArticleCell reports2023
Neddylation is required for perinatal cardiac development through stimulation of metabolic maturation.
Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- The maternal gut microbiota influences myocardial maturation and diastolic function of offspring in mice.Science China. Life sciences · 2026Article
- COP9 signalosome deneddylation activity is required for proliferation but not dedifferentiation of vascular smooth muscle cells in neointimal hyperplasia.American journal of physiology. Heart and circulatory physiology · 2026Article
- Lactylation, Crotonylation and Succinylation: Decoding Their Roles in the Progression of Cardiovascular Disease.Reviews in cardiovascular medicine · 2026Review
- Molecular gatekeepers of endogenous adult mammalian cardiomyocyte proliferation.Nature reviews. Cardiology · 2025Review
- Molecular choreography of E1 enzymes in ubiquitin-like protein cascades: New insights into dynamics and specificity.The Journal of biological chemistry · 2025Review
- Ubiquitination regulation of mitochondrial homeostasis: a new sight for the treatment of gastrointestinal tumors.Frontiers in immunology · 2025Review
- Neddylation drives myofibrillogenesis in the developing heart.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Inhibition of cardiomyocyte neddylation impairs embryonic cardiac morphogenesis.Journal of molecular and cellular cardiology · 2024Article
- Neddylation steers the fate of cellular receptors.Experimental & molecular medicine · 2024Review
- Ubiquitin Ligase RBX2/SAG Regulates Mitochondrial Ubiquitination and Mitophagy.Circulation research · 2024Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Review
- New insights into SUMOylation and NEDDylation in fibrosis.Frontiers in pharmacology · 2024Review
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Cardiac maturation is crucial for postnatal cardiac development and is increasingly known to be regulated by a series of transcription factors. However, post-translational mechanisms regulating this process remain unclear. Here we report the indispensable role of neddylation in cardiac maturation. Mosaic deletion of NAE1, an essential enzyme for neddylation, in neonatal hearts results in the rapid development of cardiomyopathy and heart failure. NAE1 deficiency disrupts transverse tubule formation, inhibits physiological hypertrophy, and represses fetal-to-adult isoform switching, thus culminating in cardiomyocyte immaturation. Mechanistically, we find that neddylation is needed for the perinatal metabolic transition from glycolytic to oxidative metabolism in cardiomyocytes. Further, we show that HIF1α is a putative neddylation target and that inhibition of neddylation accumulates HIF1α and impairs fatty acid utilization and bioenergetics in cardiomyocytes. Together, our data show neddylation is required for cardiomyocyte maturation through promoting oxidative metabolism in the developing heart.
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