Mitochondrial carrier SLC25A19 is required for respiratory chain function
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1064929 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27553864_1.fastq.gz | Fastqsanger.gz | |||
| SRR27553864_2.fastq.gz | Fastqsanger.gz | |||
| SRR27553865_1.fastq.gz | Fastqsanger.gz | |||
| SRR27553865_2.fastq.gz | Fastqsanger.gz | |||
| SRR27553866_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 18 |
Similar Datasets
Project description:In this study, we investigate how mitochondrial thiamine pyrophosphate (TPP) transporter SLC25A19 regulates mitochondrial function and cell metabolism.
2025-03-31 | GSE253270 | GEO
Project description:To understand the common and opposite effects of mitochondrial and lysosomal perturbations on cellular signaling, we performed RNAseq in HeLa cells stably silenced for the mitochondrial respiratory chain subunit UQCRC1 (as a model of chronic mitochondrial respiratory chain deficiency), for lysosomal hydrolase acid alpla-glucosidase (GAA), or for lysosomal cathepsin B (CTSB). The controls were HeLa cells with scrambled shRNA.
2024-05-24 | GSE256471 | GEO
Project description:Mitochondrial dysfunction induces a strong adaptive retrograde signaling response, however many of the down-stream effectors remain to be discovered. Here, we studied the shared transcriptional responses to three different mitochondrial respiratory chain inhibitors in human primary skin fibroblasts using QuantSeq 3’RNA-sequencing. We found that mevalonate pathway genes were concurrently downregulated irrespective of the respiratory chain complex affected. Targeted metabolomics demonstrated that impaired mitochondrial respiration at any of the three affected complexes also had functional consequences on the mevalonate pathway, reducing cholesterol precursor metabolites. A deeper study of complex I inhibition showed a reduced activity of ER-bound sterol sensing enzymes through impaired processing of the transcription factor SREBP2 and accelerated degradation of the ER cholesterol sensors SQLE and HMGCR. These adaptations of mevalonate pathway activity neither affected total intracellular cholesterol levels nor the cellular free (non-esterified) cholesterol pool. Measurement of intracellular cholesterol using the fluorescent cholesterol binding dye filipin revealed that complex I inhibition elevated cholesterol on intracellular compartments. Our study shows that mitochondrial respiratory chain dysfunction elevates intracellular free cholesterol levels and therefore attenuates the expression of mevalonate pathway enzymes, which lowers endogenous cholesterol biosynthesis, disrupting the metabolic output of the mevalonate pathway. Intracellular disturbances in cholesterol homeostasis may alter systemic cholesterol management in diseases associated with declining mitochondrial function.
2022-02-25 | GSE191034 | GEO
Project description:Primary mitochondrial respiratory chain (RC) diseases are heterogeneous in etiology and manifestations but collectively impair cellular energy metabolism. To identify a common cellular response to RC disease, systems biology level transcriptome investigations were performed in human RC disease skeletal muscle and fibroblasts. Global transcriptional and post-transcriptional dysregulation in a tissue-specific fashion was identified across diverse RC complex and genetic etiologies. RC disease muscle was characterized by decreased transcription of cytosolic ribosomal proteins to reduce energy-intensive anabolic processes, increased transcription of mitochondrial ribosomal proteins, shortened 5'-UTRs to improve translational efficiency, and stabilization of 3'-UTRs containing AU-rich elements. These same modifications in a reversed direction typified RC disease fibroblasts. RC disease also dysregulated transcriptional networks related to basic nutrient-sensing signaling pathways, which collectively mediate many aspects of tissue-specific cellular responses to primary RC disease. These findings support the utility of a systems biology approach to improve mechanistic understanding of mitochondrial RC disease. To identify a common cellular response to primary RC that might improve mechanistic understanding and lead to targeted therapies for human RC disease, we performed collective transcriptome profiling in skeletal muscle biopsy specimens and fibroblast cell lines (FCLs) of a diverse cohort of human mitochondrial disease subjects relative to controls. Systems biology investigations of common cellular responses to primary RC disease revealed a collective pattern of transcriptional, post-transcriptional and translational dysregulation occurring in a highly tissue-specific fashion. Affymetrix Human Exon 1.0ST microarray analysis was performed on 29 skeletal muscle samples and Fibroblast cell lines from mitochondrial disease patients and age- and gender-matched controls.
2013-07-01 | E-GEOD-42986 | biostudies-arrayexpress
Project description:Accumulation of mitochondrial DNA (mtDNA) deletions to detrimental levels in few cells and chronic inflammation are concomitant during aging in many tissues, thus raising the question of a causal link between both phenomena. To approach this, we generated mice which accumulate such deletions in the epidermis by expression of a mutant TWINKLE helicase in keratinocytes. These short-lived mice showed a severe depletion of mtDNA, as well as low amounts of large-scale deletions in the epidermis. These alterations led to an imbalanced stoichiometry of mitochondrial respiratory chain complexes, inducing a unique combination of cytokine expression in the epidermis. This caused a severe inflammatory phenotype, with massive immune cell infiltrates already before birth, resulting in serous scabs at the ventral skin region and limb joints. Altogether, these data suggest that severe respiratory chain dysfunction, as observed in a few cells in aged tissues, might be involved in the development of chronic inflammation.
2017-08-16 | GSE97242 | GEO
Project description:In childhood skeletal growth is driven by transient expansion of cartilage in the growth plate. Common belief is that energy production in this hypoxic tissue mainly relies on anaerobic glycolysis and not on mitochondrial respiratory chain (RC) activity. However, children with mitochondrial diseases causing RC dysfunction often present with short stature, which indicates that RC activity may be essential for cartilage-mediated skeletal growth. To elucidate the role of the mitochondrial RC in cartilage growth and pathology, we generated mice with impaired RC-function in cartilage. These mice develop normally until birth, but their later growth is retarded. A detailed molecular analysis revealed that metabolic signaling and extracellular matrix formation is disturbed and induces cell death at the cartilage-bone junction to cause a chondrodysplasia-like phenotype. Hence, the results demonstrate the overall importance of the metabolic switch from fetal glycolysis to postnatal RC activation in growth plate cartilage and explain why RC dysfunction can cause short stature in children with mitochondrial disease
2019-04-24 | GSE130191 | GEO
Project description:Primary mitochondrial respiratory chain (RC) diseases are heterogeneous in etiology and manifestations but collectively impair cellular energy metabolism. To identify a common cellular response to RC disease, systems biology level transcriptome investigations were performed in human RC disease skeletal muscle and fibroblasts. Global transcriptional and post-transcriptional dysregulation in a tissue-specific fashion was identified across diverse RC complex and genetic etiologies. RC disease muscle was characterized by decreased transcription of cytosolic ribosomal proteins to reduce energy-intensive anabolic processes, increased transcription of mitochondrial ribosomal proteins, shortened 5'-UTRs to improve translational efficiency, and stabilization of 3'-UTRs containing AU-rich elements. These same modifications in a reversed direction typified RC disease fibroblasts. RC disease also dysregulated transcriptional networks related to basic nutrient-sensing signaling pathways, which collectively mediate many aspects of tissue-specific cellular responses to primary RC disease. These findings support the utility of a systems biology approach to improve mechanistic understanding of mitochondrial RC disease. To identify a common cellular response to primary RC that might improve mechanistic understanding and lead to targeted therapies for human RC disease, we performed collective transcriptome profiling in skeletal muscle biopsy specimens and fibroblast cell lines (FCLs) of a diverse cohort of human mitochondrial disease subjects relative to controls. Systems biology investigations of common cellular responses to primary RC disease revealed a collective pattern of transcriptional, post-transcriptional and translational dysregulation occurring in a highly tissue-specific fashion.
2013-07-01 | GSE42986 | GEO
Project description:Respiratory chain inactivation links cartilage-mediated growth retardation to mitochondrial diseases
| PRJNA534258 | ENA
Project description:Mitochondrial respiratory chain dysfunction alters ER sterol sensing and mevalonate pathway activity
| PRJNA789485 | ENA
Project description:Hundreds of genes have been associated with respiratory chain disease so far. Elimination of the respiratory electron chain by depleting the entire mitochondrial DNA (mtDNA, ��0 cells) has therefore one of the most severe impacts on the energy metabolism in eukaryotic cells. Here, we integrated proteomic data sets including the post transcriptional modifications (PTM���s) phosphorylation and ubiquitination, with metabolomic data sets and selected enzyme activities in the osteosarcoma cell line 143B.TK-. We applied a shotgun based SILAC LC-MS proteomics and a targeted metabolomics approach to elucidate the consequences of the ��0 state. Pathway analysis revealed a non-uniform down-regulation of the respiratory electron chain, the tricarboxylic acid (TCA) cycle and the pyruvate metabolism in ��0 cells. Surprisingly, some metabolites of the TCA cycle were dramatically reduced in ��0 cells, like citric acid (100-fold) and aconitic acid (6-fold), others instead increased, like succinic and fumaric acid (5-fold). Enzyme activities were xy. Exceptionally, the mitochondrial retrograde response, a pathway of communication from mitochondria to the nucleus, was up-regulated in ��0 cells, like signalling by GPCR, EGFR, G12/13 alpha cAMP and RhoGTPase. We observed a striking de-ubiquitination of 80S ribosomal proteins (3-fold) and SLC amino acid transporters (7-fold) in ��0 cells, the later might cause the observed significant increase of amino acids levels in ��0 cells. We conclude that mtDNA depletion not only leads to an uneven down-regulation of mitochondrial energy pathways, but also to a strong retrograde response. The partly collapsed TCA cycle and de-ubiquitination of SLC transporters lead to an altered amino acid metabolism.
2022-02-22 | PXD002270 | Pride