The mitochondrial citrate carrier: a new player in inflammation.

Biochem J

Department of Pharmaco-Biology, Laboratory of Biochemistry and Molecular Biology, University of Bari, 70125 Bari, Italy.

Published: September 2011

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.

Download full-text PDF

Source
http://dx.doi.org/10.1042/BJ20111275DOI Listing

Publication Analysis

Top Keywords

citrate carrier
8
cic
5
mitochondrial citrate
4
carrier player
4
player inflammation
4
inflammation mitochondrial
4
mitochondrial cic
4
cic citrate
4
carrier catalyses
4
catalyses efflux
4

Similar Publications

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.

View Article and Find Full Text PDF

Why and how citrate may sensitize malignant tumors to immunotherapy.

Drug Resist Updat

January 2025

Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Cité, Paris 75014, France. Electronic address:

Article Synopsis
  • Immunotherapy, particularly when combined with chemotherapy, has shown limited effectiveness against solid tumors due to factors like cancer cells promoting immune cell exhaustion through nutrient diversion in the tumor microenvironment (TME).
  • The authors suggest using high doses of sodium citrate (SCT) alongside immune checkpoint inhibitors (ICIs) to inhibit cancer cell metabolism and enhance anti-tumor immune responses, as preclinical studies indicate SCT can reduce cancer growth and improve chemotherapy outcomes.
  • SCT works by increasing available glucose for immune cells and lowering lactic acid levels in the TME, which may enhance T cell activity and repolarize macrophages, indicating its potential to significantly boost the effectiveness of current immunotherapies in clinical settings.
View Article and Find Full Text PDF

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 PDF

A hierarchical hepatic de novo lipogenesis substrate supply network utilizing pyruvate, acetate, and ketones.

Cell 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 PDF

Breeding for an elite malting barley cultivar with acid soil tolerance.

Commun 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.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!