The mitochondrial citrate carrier SLC25A1 regulates metabolic reprogramming and morphogenesis in the developing heart.

ABSTRACT: 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-depen

SUBMITTER: Ohanele C 

PROVIDER: S-EPMC11528069 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature