The mitochondrial citrate carrier SLC25A1 regulates metabolic reprogramming and morphogenesis in the developing heart.
Animals
Morphogenesis
/ genetics
Mice
Mice, Knockout
Heart
/ embryology
Anion Transport Proteins
/ metabolism
Mitochondria
/ metabolism
Gene Expression Regulation, Developmental
Heart Defects, Congenital
/ genetics
Mitochondria, Heart
/ metabolism
Female
Mitochondrial Proteins
/ metabolism
Metabolic Reprogramming
Carrier Proteins
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
31 Oct 2024
31 Oct 2024
Historique:
received:
28
12
2023
accepted:
21
10
2024
medline:
1
11
2024
pubmed:
1
11
2024
entrez:
1
11
2024
Statut:
epublish
Résumé
The developing mammalian heart undergoes an important metabolic shift from glycolysis towards mitochondrial oxidation that is critical to support the increasing energetic demands of the maturing heart. Here, we describe a new mechanistic link between mitochondria and cardiac morphogenesis, uncovered by studying mitochondrial citrate carrier (SLC25A1) knockout mice. Slc25a1 null embryos displayed impaired growth, mitochondrial dysfunction and cardiac malformations that recapitulate the congenital heart defects observed in 22q11.2 deletion syndrome, a microdeletion disorder involving the SLC25A1 locus. Importantly, Slc25a1 heterozygous embryos, while overtly indistinguishable from wild type, exhibited an increased frequency of these defects, suggesting Slc25a1 haploinsuffiency and dose-dependent effects. Mechanistically, SLC25A1 may link mitochondria to transcriptional regulation of metabolism through epigenetic control of gene expression to promote metabolic remodeling in the developing heart. Collectively, this work positions SLC25A1 as a novel mitochondrial regulator of cardiac morphogenesis and metabolic maturation, and suggests a role in congenital heart disease.
Identifiants
pubmed: 39482367
doi: 10.1038/s42003-024-07110-8
pii: 10.1038/s42003-024-07110-8
doi:
Substances chimiques
citrate-binding transport protein
0
Anion Transport Proteins
0
Mitochondrial Proteins
0
Carrier Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1422Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : R01-GM-144729
Organisme : U.S. Department of Defense (United States Department of Defense)
ID : 0000063651
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : 1RF1AG060285
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R00-HL-141702
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R01-HL144776
Organisme : U.S. Department of Health & Human Services | NIH | NIH Office of the Director (OD)
ID : S10OD021748
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : P30CA138292
Informations de copyright
© 2024. The Author(s).
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