biostudies-literatureOhanele CU.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)NCATS NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of General Medical SciencesNIA NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)Additional Ventures Single Ventricle Research Fund Georgia Clinical and Translational Science Alliance of NIHNHLBI NIH HHSU.S. Department of Health & Human Services | NIH | NIH Office of the DirectorU.S. Department of Health & Human Services | National Institutes of Health (NIH)U.S. Department of Health & Human Services | NIH | NIH Office of the Director (OD)U.S. Department of Health & Human Services | NIH | National Cancer InstituteU.S. Department of DefenseU.S. Department of Defense (United States Department of Defense)NCI NIH HHSU.S. Department of Health & Human Services | National Institutes of HealthNIH HHSNIGMS NIH HHS1422https://www.ebi.ac.uk/biostudies/studies/S-EPMC11528069biostudies-literatureUnknown7(1)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-depenCommunications biologyThe mitochondrial citrate carrier SLC25A1 regulates metabolic reprogramming and morphogenesis in the developing heart.PMC11528069UL1 TR000454RF1 AG060285R00 HL141702R00-HL-141702R01 GM144729R01-GM-1447290000063651R01 HL144776P30 CA138292P30CA1382921RF1AG060285S10 OD021748R01-HL144776S10OD021748Ohanele CGayle ADSohani FDavis MEKarlstaedt AGhazal NGeiger JTFaundez VPorter GAPeoples JNKwong JQBrown MEfalseThe mitochondrial citrate carrier SLC25A1 regulates metabolic reprogramming and morphogenesis in the developing heart.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-depen2024-01-01T00:00:00Z2024 Oct2026-07-15T04:01:18.935Z2025-04-04T00:26:34.437ZS-EPMC115280693948236710.1038/s42003-024-07110-8