Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Global transcriptional response of Saccharomyces cerevisiae following the deletion of succinate dehydrogenase

ABSTRACT: Background Mitochondrial respiration is an important and widely conserved cellular function in eukaryotic cells. The succinate dehydrogenase complex (SDH-complex) plays an important role in respiration as it connects the mitochondrial respiratory chain to the tricarboxylic acid (TCA) cycle where it catalyzes the oxidation of succinate to fumarate. Cellular response to the SDH-complex dysfunction (i.e. impaired respiration) thus has important implications not only for biotechnological applications but also for understanding cellular physiology underlying metabolic diseases such as diabetes. We therefore explored the physiological and transcriptional response of Saccharomyces cerevisiae to the deletion of SDH3, that codes for an essential subunit of the SDH-complex. Results Although the SDH-complex has no direct role in transcriptional regulation and the flux through the corresponding reaction under the studied conditions is very low, deletion of SDH3 resulted in significant changes in the expression of several genes involved in various cellular processes ranging from metabolism to the cell-cycle. By using various bioinformatics tools we explored the organization of these transcriptional changes in the metabolic and other cellular functional interaction networks. Conclusions Our results show that the transcriptional regulatory response resulting from the impaired respiratory function is linked to several different parts of the metabolism, including fatty acid and sterol metabolism.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE13924 | GEO | 2008/12/16

SECONDARY ACCESSION(S): PRJNA110253

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcription profiling of S. cerevisiae following the deletion of succinate dehydrogenase

Project description:Background; Mitochondrial respiration is an important and widely conserved cellular function in eukaryotic cells. The succinate dehydrogenase complex (SDH-complex) plays an important role in respiration as it connects the mitochondrial respiratory chain to the tricarboxylic acid (TCA) cycle where it catalyzes the oxidation of succinate to fumarate. Cellular response to the SDH-complex dysfunction (i.e. impaired respiration) thus has important implications not only for biotechnological applications but also for understanding cellular physiology underlying metabolic diseases such as diabetes. We therefore explored the physiological and transcriptional response of Saccharomyces cerevisiae to the deletion of SDH3, that codes for an essential subunit of the SDH-complex. Results; Although the SDH-complex has no direct role in transcriptional regulation and the flux through the corresponding reaction under the studied conditions is very low, deletion of SDH3 resulted in significant changes in the expression of several genes involved in various cellular processes ranging from metabolism to the cell-cycle. By using various bioinformatics tools we explored the organization of these transcriptional changes in the metabolic and other cellular functional interaction networks. Conclusions; Our results show that the transcriptional regulatory response resulting from the impaired respiratory function is linked to several different parts of the metabolism, including fatty acid and sterol metabolism. Experiment Overall Design: Two replicates for sdh3 deletion mutants. Reference strain transcriptome data: Westergaard SL et al., FEMS Yeast Res 2004, 5: 193-204.

2009-01-13 | E-GEOD-13924 | biostudies-arrayexpress

Succinate dehydrogenase (SDH)-Complex II regulates skeletal muscle cellular respiration and fatigue but not muscle mass in genetically induced pulmonary emphysema [20 wk]

Project description:Skeletal muscle wasting and reduced oxidative capacity coexist in patients with COPD/pulmonary emphysema and are independently associated with higher mortality. Whether reduced respiration contributes to muscle atrophy in that setting remains unknown. We have previously shown that a mouse with genetically induced COPD/pulmonary emphysema recapitulates muscle dysfunction features present in patients’ muscles, including reduced expression and activity of succinate dehydrogenase (SDH), which are partially reversed by genetic gain of SDH function. Previous research suggests that succinate accumulation, a by-product of SDH inhibition, can increase respiratory capacity of skeletal muscle. Here, we generated an inducible, muscle-specific SDH-C knockout mouse which demonstrates lower mitochondrial oxygen consumption and oxidative fibers’ contractility, associated with overall reduced exercise endurance. These changes are partially offset by mitochondrial complex I-dependent respiration, a respiratory pattern replicated in the muscles from the COPD/pulmonary emphysema genetic model. Moreover, while mice skeletal muscle SDH-C knockout causes an early succinate accumulation associated with a downregulated transcriptome, these changes do not correlate with the proteomic landscape; and animals muscle mass, fiber-type composition, and dry body mass constituents remain unaltered. We preset the first conditional, skeletal muscle-specific SDH-C knockout animal and demonstrate that while SDH-C regulates fibers respiration in genetically induced pulmonary emphysema, it does not control muscle mass.

2024-02-24 | GSE255635 | GEO

Succinate dehydrogenase (SDH)-Complex II regulates skeletal muscle cellular respiration and fatigue but not muscle mass in genetically induced pulmonary emphysema [3 wk]

2024-02-24 | GSE255632 | GEO

Gene expression analysis of SDH-deficient immortalized kidney epithelial cells

Project description:Succinate dehydrogenase (SDH) is a mitochondrial protein complex responsible for the oxidation of succinate to fumarate in the tricarboxylic acid cycle. Loss-of-function mutations in any of the SDH genes are associated with susceptibility to develop neu-roendrocrine neoplasms and renal cell carcinoma. However, the impact of SDH loss on cell metabolism and the mechanisms enabling growth of SDH-defective cells are largely unexplored. To address this issue we generated Sdhb-ablated kidney mouse cells and compared their transcriptomic profile with that of Sdhb-proficient cells. Results of this gene analysis are provided in the here deposited gene array.

2016-01-22 | E-MTAB-4349 | biostudies-arrayexpress

SDH deficiency-driven succinate accumulation dictates the drug resistance of AML through regulating p-UBC12/cullin activity

Project description:Drug resistance is vital for the poor prognosis of acute myeloid leukemia (AML) patients, but the underlying mechanism remains poorly understood. Given the unique microenvironment of bone marrow, we reasoned that drug resistance of AML might rely on distinct microenvironment-associated metabolic processes. Here, we identified SDH deficiency and over-cumulative succinate as typical features in AML, with a marked function in causing the resistance of AML cells to a wide range of anti-cancer therapies. Mechanistically, succinate promoted the accumulation of oncogenic proteins in a manner that precedes transcriptional activation. This function was mediated by succinate-triggered upregulation of UBC12 phosphorylation, which impaired its E2 function in cullins neddylation. Notably, decreasing succinate levels by fludarabine could effectively restore the drug sensitivity of SDH-deficient AML PDX. Together, we uncover a novel function of succinate in driving drug resistance by regulating p-UBC12/cullin activity, and indicate reshaping succinate metabolism as a promising treatment for SDH-deficient AML.

2024-08-28 | PXD053722 | Pride

SDH deficiency-driven succinate accumulation dictates the drug resistance of AML through regulating p-UBC12/cullin activity

2024-08-28 | PXD047175 | Pride

Succinate dehydrogenase deficiency-driven succinate accumulation induces drug resistance in acute myeloid leukemia via ubiquitin-cullin regulation

2024-08-27 | GSE247623 | GEO

Expression data from SDH-disabled GIST

Project description:Pediatric GIST commonly harbors a disabled succinate dehydrogenase complex (SDH), which yields tumors with highly conserved genomes but characteristic epigenomic signatures. Mysteriously, nearly half of such SDH-deficient GIST, including tumors from Carney Triad patients, lack identifiable mutations in SDH component genes and genes required for complex assembly (SDHA, SDHB, SDHC, SDHD, SDHAF, termed SDHx). Genomic sequencing coupled with DNA methylation and transcriptional profiling have exposed SDHC promoter-specific CpG island epimutation and concomitant gene silencing in the majority of SDHx-WT GIST.

2015-01-02 | GSE56670 | GEO

Expression data from SDH-disabled GIST

2015-01-02 | E-GEOD-56670 | biostudies-arrayexpress

Myc-mediated SDHA Acetylation Triggers Epigenetic Regulation of Gene Expression and Tumorigenesis

Project description:Trimethylated H3K4 (H3K4me3), which is often found surrounding the transcriptional start site of active genes, is strongly enriched in the promoter regions of Myc-targeted genes. Succinate, which inhibits JmjC domain-containing histone demethylases (JHDMs), can induce H3K4me3 level of the promoter regions. It's interesting to ask whether Myc can mediate H3K4me3 by inhibiting SDH activity and inducing cellular succinate level. Here, We used ChIP-seq to study Myc modulates H3K4me3 by altering succinate levels, dimethyl succinate (DMS), a membrane-permeable succinate analog, was introduced to treat P493-6 cells with high or depleted Myc expression. And we performed RNA-seq assays in Myc expressed or depleted P493-6 cells with or without DMS treatment. Besides, we also performed RNA-seq assays in Myc expressed or depleted P493-6 cells with or without 3-nitropropionic acid (3-NPA, SDH enzyme inhibitor) treatment.

2020-03-18 | GSE124255 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data