Journal article
Neddylation is required for perinatal cardiac development through stimulation of metabolic maturation
Cell reports (Cambridge), Vol.42(1), 112018
01/31/2023
DOI: 10.1016/j.celrep.2023.112018
PMCID: PMC10029150
PMID: 36662623
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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•Inhibition of neddylation in the developing heart causes heart failure•Neddylation is required for cardiomyocyte maturation•Neddylation regulates cardiomyocyte perinatal metabolic reprogramming•Neddylation targets HIF1α and promotes fatty acid utilization in cardiomyocytes
Zou et al. investigate the role of neddylation, a protein modification process, in the development and maturation of the heart during the perinatal stage. The results suggest that neddylation plays a crucial role in heart cell maturation and postnatal cardiac development by regulating the switch between glycolysis and oxidative metabolism.
Details
- Title: Subtitle
- Neddylation is required for perinatal cardiac development through stimulation of metabolic maturation
- Creators
- Jianqiu Zou - Augusta UniversityWenjuan Wang - Augusta UniversityYi Lu - Augusta UniversityJuan Ayala - Augusta UniversityKunzhe Dong - Augusta UniversityHongyi Zhou - Augusta UniversityJinxi Wang - University of IowaWeiqin Chen - Augusta UniversityNeal L. Weintraub - Augusta UniversityJiliang Zhou - University of IowaJie Li - Augusta UniversityHuabo Su - Augusta University
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.42(1), 112018
- DOI
- 10.1016/j.celrep.2023.112018
- PMID
- 36662623
- PMCID
- PMC10029150
- NLM abbreviation
- Cell Rep
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: R01HL124248, R01HL146807A1, R01HL165205; DOI: 10.13039/100000968, name: American Heart Association, award: 16SDG30940002, 17POST33410592, 19CDA34760311, 19TPA34880050
- Language
- English
- Date published
- 01/31/2023
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984446720802771
Metrics
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