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Neddylation is required for perinatal cardiac development through stimulation of metabolic maturation

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. M...

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Autores principales: Zou, Jianqiu, Wang, Wenjuan, Lu, Yi, Ayala, Juan, Dong, Kunzhe, Zhou, Hongyi, Wang, Jinxi, Chen, Weiqin, Weintraub, Neal L., Zhou, Jiliang, Li, Jie, Su, Huabo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10029150/
https://www.ncbi.nlm.nih.gov/pubmed/36662623
http://dx.doi.org/10.1016/j.celrep.2023.112018
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author Zou, Jianqiu
Wang, Wenjuan
Lu, Yi
Ayala, Juan
Dong, Kunzhe
Zhou, Hongyi
Wang, Jinxi
Chen, Weiqin
Weintraub, Neal L.
Zhou, Jiliang
Li, Jie
Su, Huabo
author_facet Zou, Jianqiu
Wang, Wenjuan
Lu, Yi
Ayala, Juan
Dong, Kunzhe
Zhou, Hongyi
Wang, Jinxi
Chen, Weiqin
Weintraub, Neal L.
Zhou, Jiliang
Li, Jie
Su, Huabo
author_sort Zou, Jianqiu
collection PubMed
description 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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spelling pubmed-100291502023-03-21 Neddylation is required for perinatal cardiac development through stimulation of metabolic maturation Zou, Jianqiu Wang, Wenjuan Lu, Yi Ayala, Juan Dong, Kunzhe Zhou, Hongyi Wang, Jinxi Chen, Weiqin Weintraub, Neal L. Zhou, Jiliang Li, Jie Su, Huabo Cell Rep Article 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. 2023-01-31 2023-01-19 /pmc/articles/PMC10029150/ /pubmed/36662623 http://dx.doi.org/10.1016/j.celrep.2023.112018 Text en https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Zou, Jianqiu
Wang, Wenjuan
Lu, Yi
Ayala, Juan
Dong, Kunzhe
Zhou, Hongyi
Wang, Jinxi
Chen, Weiqin
Weintraub, Neal L.
Zhou, Jiliang
Li, Jie
Su, Huabo
Neddylation is required for perinatal cardiac development through stimulation of metabolic maturation
title Neddylation is required for perinatal cardiac development through stimulation of metabolic maturation
title_full Neddylation is required for perinatal cardiac development through stimulation of metabolic maturation
title_fullStr Neddylation is required for perinatal cardiac development through stimulation of metabolic maturation
title_full_unstemmed Neddylation is required for perinatal cardiac development through stimulation of metabolic maturation
title_short Neddylation is required for perinatal cardiac development through stimulation of metabolic maturation
title_sort neddylation is required for perinatal cardiac development through stimulation of metabolic maturation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10029150/
https://www.ncbi.nlm.nih.gov/pubmed/36662623
http://dx.doi.org/10.1016/j.celrep.2023.112018
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