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Impact of mitochondrial citrate carrier expression on metabolism in the developing heart

ABSTRACT: Impact of mitochondrial citrate carrier expression on metabolism in the developing heart

PROVIDER: PRJNA1171813 | ENA |

REPOSITORIES: ENA

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Impact of mitochondrial citrate carrier expression on metabolism in the developing heart

Project description:Slc25a1 encodes for the mitochondrial citrate carrier, a mitochondrial inner membrane transporter that mediates mitochondrial citrate export. Systemic deletion of Slc25a1 (both homozygous and heterozygous loss) leads to cardiac structural defects and mitochondrial dysfunction. Transcriptomic profiles of metabolic gene expression in the the developing mouse heart at E17.5 reveal alterations in metabolic pathways including oxdiative phosphorylation, supporting mitochondrial structural and functional defects observed with loss of this transporter.

2024-10-11 | GSE279295 | GEO

Mitochondrial citrate metabolism and efflux regulates trophoblast differentiation

Project description:Cytotrophoblasts fuse to form and renew syncytiotrophoblasts necessary to maintain placental health throughout gestation. During cytotrophoblast to syncytiotrophoblast differentiation, cells undergo regulated metabolic and transcriptional reprogramming. Mitochondria play a critical role in differentiation events in cellular systems, thus we hypothesized that mitochondrial metabolism played a central role in trophoblast differentiation. In this work, we employed static and stable isotope tracing untargeted metabolomics methods together with gene expression and histone acetylation studies in an established cell culture model of trophoblast differentiation. Trophoblast differentiation was associated with increased abundance of the TCA cycle intermediates citrate and α-ketoglutarate. Citrate was preferentially exported from mitochondria in the undifferentiated state but was retained to a larger extent within mitochondria upon differentiation. Correspondingly, differentiation was associated with decreased expression of the mitochondrial citrate transporter (CIC). CRISPR/Cas9 disruption of the mitochondrial citrate carrier showed that CIC is required for biochemical differentiation of trophoblast. Loss of CIC resulted in broad alterations in gene expression and histone acetylation. These gene expression changes were partially rescued through acetate supplementation. Taken together, these results highlight a central role for mitochondrial citrate metabolism in the orchestration of histone acetylation and gene expression during trophoblast differentiation.

2023-05-05 | GSE223514 | GEO

The ageing epigenome regulates stem cell fate via mitochondrial-derived vesicles delivery of citrate carrier to lysosomes [CUT&RUN_H3AC]

Project description:We report that upon ageing MSC exhibit reduced metabolic rates, with lower lipid biosynthesis and elevated acetyl-CoA levels. However, aged cells display chromatin compaction and histone hypo-acetylation, particularly on enhancers of genes involved in osteogenesis. This is due to the lower levels of citrate carrier, resulting in impaired acetyl-CoA export from mitochondria to the cytosol, which concomitantly affects histone acetylation and osteogenesis. CiC gets degraded in the aged cells via an MVD-lysosomal pathway, which establishes a strong connection between mitochondrial quality control, chromatin and stemness.

2021-07-08 | GSE173358 | GEO

The ageing epigenome regulates stem cell fate via mitochondrial-derived vesicles delivery of citrate carrier to lysosomes [CUT&RUN]

2021-07-08 | GSE155714 | GEO

Mitochondrial citrate metabolism and efflux regulates trophoblast differentiation

Project description:Mitochondrial citrate metabolism and efflux regulates trophoblast differentiation

| PRJNA926624 | ENA

The ageing epigenome regulates stem cell fate via mitochondrial-derived vesicles delivery of citrate carrier to lysosomes [CUT&RUN]

Project description:The ageing epigenome regulates stem cell fate via mitochondrial-derived vesicles delivery of citrate carrier to lysosomes [CUT&RUN]

| PRJNA655347 | ENA

The ageing epigenome regulates stem cell fate via mitochondrial-derived vesicles delivery of citrate carrier to lysosomes [CUT&RUN_H3AC]

Project description:The ageing epigenome regulates stem cell fate via mitochondrial-derived vesicles delivery of citrate carrier to lysosomes [CUT&RUN_H3AC]

| PRJNA725237 | ENA

Carrier Subclass

Project description:Carrier Subclass

| PRJNA1031099 | ENA

Toll-like receptor signaling rewires macrophage metabolism and promotes histone acetylation via ATP-citrate lyase

Project description:TLR activation induces inflammatory responses in macrophages by activating temporally defined transcriptional cascades within the first hours after stimulation. Whether concurrent changes in the cellular metabolism that occur upon TLR activation influence the quality of the transcriptional responses remain unknown. Here we investigated how macrophages adopt their metabolism early after activation to regulate TLR-inducible gene induction. Macrophages increase glucose metabolism and adopt fluxes through the TCA cycle to foster Citrate synthesis. We concomitantly observe activation of ATP-Citrate Lyase (Acly), resulting in augmented acetyl-CoA synthesis and histone acetylation. To investigate which genes and genes classes require ATP-citrate lyase activity for induction we stimulated bone marrow derived macrophages with LPS after ATP-citrate lyase inhibition.

2019-12-16 | GSE129497 | GEO

Severe Neonatal Presentation of Mitochondrial Citrate Carrier (SLC25A1) Deficiency.

Project description:Mutations of the mitochondrial citrate carrier (CIC) SLC25A1 cause combined D-2- and L-2-hydroxyglutaric aciduria (DL-2HGA; OMIM #615182), a neurometabolic disorder characterized by developmental delay, hypotonia, and seizures. Here, we describe the female child of consanguineous parents who presented neonatally with lactic acidosis, periventricular frontal lobe cysts, facial dysmorphism, recurrent apneic episodes, and deficient complex IV (cytochrome c oxidase) activity in skeletal muscle. Exome sequencing revealed a homozygous SLC25A1 missense mutation [NM_005984.4: c.593G>A; p.(Arg198His)] of a ubiquitously conserved arginine residue putatively situated within the substrate-binding site I of CIC. Retrospective review of the patient's organic acids confirmed the D- and L-2-hydroxyglutaric aciduria typical of DL-2HGA to be present, although this was not appreciated on initial presentation. Cultured patient skin fibroblasts showed reduced survival in culture, diminished mitochondrial spare respiratory capacity, increased glycolytic flux, and normal mitochondrial bulk, inner membrane potential, and network morphology. Neither cell survival nor cellular respiratory parameters were improved by citrate supplementation, although oral citrate supplementation did coincide with amelioration of lactic acidosis and apneic attacks in the patient. This is the fifth clinical report of CIC deficiency to date. The clinical features in our patient suggest that this disorder, which can potentially be recognized either by molecular means or based on its characteristic organic aciduria, should be considered in the differential diagnosis of pyruvate dehydrogenase deficiency and respiratory chain disorders. One-Sentence Summary A novel homozygous missense substitution in SLC25A1 was identified in a neonate presenting with lactic acidosis, intracerebral cysts, and an apparent mitochondrial complex IV defect in muscle.

| S-EPMC5110450 | biostudies-literature

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