The mitochondrial CIC (citrate carrier) catalyses the efflux of citrate from the mitochondrial matrix in exchange for cytosolic malate. In the present paper we show that CIC mRNA and protein markedly increase in lipopolysaccharide-activated immune cells. Moreover, CIC gene silencing and CIC activity inhibition significantly reduce production of NO, reactive oxygen species and prostaglandins. These results demonstrate for the first time that CIC has a critical role in inflammation.
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http://dx.doi.org/10.1042/BJ20111275 | DOI Listing |
Senescent cells drive tissue dysfunction through the senescence-associated secretory phenotype (SASP). We uncovered a central role for mitochondria in the epigenetic regulation of the SASP, where mitochondrial-derived metabolites, specifically citrate and acetyl-CoA, fuel histone acetylation at SASP gene loci, promoting their expression. We identified the mitochondrial citrate carrier (SLC25A1) and ATP-citrate lyase (ACLY) as critical for this process.
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January 2025
Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Cité, Paris 75014, France. Electronic address:
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.
View Article and Find Full Text PDFCell Metab
January 2025
Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA; Fraternal Order of Eagles Diabetes Research Center (FOEDRC), University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA; FOEDRC Metabolomics Core Research Facility, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA; Holden Comprehensive Cancer Center, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA; Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA; Pappajohn Biomedical Institute, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA. Electronic address:
Hepatic de novo lipogenesis (DNL) is a fundamental physiologic process that is often pathogenically elevated in metabolic disease. Treatment is limited by incomplete understanding of the metabolic pathways supplying cytosolic acetyl-CoA, the obligate precursor to DNL, including their interactions and proportional contributions. Here, we combined extensive C tracing with liver-specific knockout of key mitochondrial and cytosolic proteins mediating cytosolic acetyl-CoA production.
View Article and Find Full Text PDFCommun Biol
September 2024
Institute of Plant Science and Resources, Okayama University, Chuo 2-20-1, Kurashiki, 710-0046, Japan.
Barley (Hordeum vulgare L.) is the fourth most produced cereal crop in the world, but its productivity on acid soil has been restricted due to its high sensitivity to aluminum (Al) toxicity. The major gene controlling Al tolerance in barley is HvAACT1 (Al-activated citrate transporter 1), which is involved in citrate secretion from the roots for Al detoxification.
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