Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The effect of accumulation of a Cit1 mutant that lacks presequence in Saccharomyces cerevisiae

ABSTRACT: Deficiencies in mitochondrial protein import are associated with a number of diseases. However, although non-imported mitochondrial proteins are at great risk of aggregation, it remains largely unclear how their accumulation causes cell dysfunction. In this study, we found that citrate synthase (Cit1) mutant that lacks the N-terminal mitochondrial targeting sequence, which we call here NdeltaCit1, is localized in the cytosol and is targeted for proteasomal degradation by the ubiquitin ligase SCFUcc1. Intriguingly, NdeltaCit1 is soluble in the cytosol and exhibits enzymatic activity. To analyze the cellular consequence of the accumulation of NdeltaCit1, we created a NdeltaCit1 mutant that escapes SCFUcc1-mediated degradation (NdeltaCit1-DS/AA). We also created a mutant that lacks the catalytic activity (NdeltaCit1-DS/AA-H/G). We performed an RNA sequence analysis and compared the gene expression profile of wild-type cells expressing NdeltaCit1-DS/AA or NdeltaCit1-DS/AA-H/G under the control of the GAL1 promoter.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE213498 | GEO | 2023/04/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Investigating B cell stimulation in ubiquilin-1 KO mice

Project description:Ubiquilins are a family of proteins involved in proteasomal degradation of mislocalized membrane proteins. Here, Greer et al. demonstrate that Ubqln1 is required for BCR-driven B cell proliferation through maintenance of protein synthesis following stimulation. In the absence of Ubqln1, mitochondrial proteins accumulate in the cytosol, which may account for the observed proteostasis. BCR stimulation of murine B cells induced a long-lasting mitochondrial depolarization that did not occur in response to LPS. We hypothesize that in the absence of Ubqln1, mitochondrial depolarization leads to an accumulation of mitochondrial membrane proteins in the cytosol, which leads to translational inhibition and a cell cycle block.

2017-11-01 | GSE86113 | GEO

Comparative analysis of transcripts from mia40-4int mutant and wild-type Saccharomyces cerevisiae strains quantified in RNA-seq experiment

Project description:The vast majority of the mitochondrial proteome originates from nuclear genes and is transported into the organelle after synthesis in the cytosol. Complex machineries, which maintain the specificity of protein import and sorting exist. Dysfunctions of mitochondrial protein sorting pathways result in diminishing specific substrate proteins, followed by systemic pathology of the organelle and organismal death. Cellular responses that are caused by slowdown in the transport of mitochondrial proteins are unknown. Here we have used RNA-seq transcription profiling of Saccharomyces cerevisiae to uncover the changes in the cellular transcriptome in the response to mitochondrial protein import dysfunction caused by mutation in the MIA40 gene. Mia40 is a key component of the mitochondrial intermembrane import and assembly (MIA) pathway. Mia40-4int mutant used in this study is not viable at high temperatures, while in the low, permissive temperature it expresses growth rate comparable to the wild-type strain. Even during the permissive temperature culture mutant cells are characterized by decreased accumulation of MIA substrate proteins. Thus permissive growth conditions were used in the present experiment to emphasise primary responses to mitochondrial protein import defect.

2015-07-31 | E-MTAB-3588 | biostudies-arrayexpress

Single-cell Landscape Analysis Reveals HSA21 Induced Regulatory Network in Mammalian Down Syndrome

Project description:Down syndrome (DS), characterized by various malfunctions, is the most common genetic chromosomal disorder. As DS population size keeps growing and most of them live beyond their puberty, their early‐onset health problems come into view. However, the molecular alterations have not been thoroughly surveyed before. Here we provide the first description of DS in single-cell resolution, including human and mouse, covering seven different organs. With 71934 mouse cells and 93207 human cells employed, we systematically revealed DS cells, across different cell types and different organs suffering from serious cellular stresses. We observed senescence stresses including ribosomal protein gene accumulation, mitochondrial dysfunction, apoptosis, and sterile inflammation in fetus DS cells. We further raised an HSA21 gene-induced regulatory network driving genome-wide expression alteration. Hence, this study provides valuable information to understand the pathological processes under DS condition.

2023-12-01 | GSE155409 | GEO

Transcription profiling of mouse splenic B cells expressing a dominant-negative p300 allele which lacks histone acetyltransferase activity

Project description:The p300 protein is one of more than 15 known mammalian HATs. We have used mice that carry a mutant allele of the p300 gene, which encodes a full-length protein that, however, lacks detectable acetyltransferase (AT)-activity and that acts in a dominant-negative manner. In addition, the allele is conditional, so that it can be expressed in a tissue-specific manner with the help of mice that express Cre-recombinase. Expression of the mutant allele specifically in B-cells, using CD19-cre mice, results in premature death with full penetrance from an autoimmune disease that closely mimics systemic lupus erythematosus (SLE) in its pathological manifestations.

2006-07-01 | E-MEXP-747 | biostudies-arrayexpress

Immune-checkpoint blockade lacks anti-tumorgenicity in NASH-induced HCC

Project description:Immune-checkpoint blockade lacks anti-tumorgenicity in NASH-induced HCC

| PRJNA671310 | ENA

Muscle transcriptome analysis of mouse models of partial trisomy and monosomy 21

Project description:Aneuploidies of human chromosome 21 (Down syndrome (DS) and monosomy 21 (M21)) lead to variable physiological abnormalities with constant mental retardation, locomotor deficits and altered muscle tone. To search for dosage-sensitive genes involved in DS and M21 phenotypes, we created two new mouse models carrying either tandem duplication (Ts2Yah) or a deletion (Ms3Yah) of the Stch-App interval homologous and syntenic with 21q11.2-q21.3 in humans. Here we report the complex mirror phenotypes of the trisomy and monosomy involving locomotion, muscle strength, mass and energetic balance that vary while ageing. Expression profiling of skeletal muscles revealed global changes in the expression of genes implicated in energetic metabolism, mitochondrial activity and biogenesis with down-regulation in Ts2Yah and up-regulation in Ms3Yah mice. The shift in skeletal muscle metabolism correlated with a change in mitochondrial proliferation without an alteration of the respiratory function. However ROS production from mitochondrial complex I decreased in Ms3Yah mice while membrane permeability of Ts2Yah mitochondria slightly increased. Our results clearly demonstrate the central versus peripheral impact of the variation of copy number of the Stch-App region on the locomotor activity, muscle biology and mitochondrial biogenesis in models of these aneuploidies. Total RNA isolated from gastrocnemius muscles of mice that are trisomic (Ts2Yah) and monosomic (Ms3Yah) for the Stch-App region on Mmu16 and diploid control mice

2015-12-31 | E-GEOD-58463 | biostudies-arrayexpress

Mitochondrial stress in GLA mutants Zebrafish is independent of globotriaosylceramide accumulation

Project description:Fabry disease (FD) is a hereditary lysosomal storage disorder caused by mutations in GLA gene resulting in reduction or lack of α-galactosidase A activity. In humans, enzymatic deficiency leads to accumulation of globotriaosylceramide (Gb3) and other glycosphingolipids in lysosomes. Current therapies focus on reversing Gb3 accumulation but fail to restore altered cellular signaling in the long run. Zebrafish (ZF) lacks Alpha 1,4-Galactosyltransferase (A4GALT) gene and cannot synthesize Gb3 or lysoGb3. We used previously generated GLA-mutant ZF model to investigate Gb3-accumulation-independent alterations by untargeted proteomics analysis of renal tissues. We observed lysosomal and mitochondrial-related pathways disfunction, higher oxidative stress, as indicated by GSH/GSSH and MDA levels, and higher antioxidant activity in mutant ZF. Moreover, mitochondrial morphological alterations also affecting cristae structure were evident. By immunohistochemistry, we also detected decreased lysosomal Tetraspanin (CD63), Superoxide dismutase 2 (SOD2), and Cadherin 1 (CDH1) protein expression. Thus, this ZF model Gb3-independently mirrors GLA mutation-related changes, and unravels novel FD pathogenic mechanisms, thereby representing a powerful tool for innovative drug screening, and the identification of markers of potential clinical relevance.

2023-10-24 | PXD035409 | Pride

Muscle transcriptome analysis of mouse models of partial trisomy and monosomy 21

2015-12-31 | GSE58463 | GEO

Proteome dysregulation in Down syndrome reveals organelle specific aberrations

Project description:Human Trisomy 21 (T21), which causes Down Syndrome (DS), is the most common known cause of intellectual disability. However, the molecular basis for DS phenotypic variability remains poorly understood. Here we used SWATH mass spectrometry (SWATH-MS) to quantify protein abundance and protein turnover in fibroblasts from a monozygotic twin pair discordant for T21, and to profile protein expression in 11 unrelated DS individuals and age-matched controls. The integration of the steady state and turnover proteomic data sets with transcript profiles indicated that protein-specific degradation of members of stoichiometric complexes presents a major determinant of T21 gene dosage outcome, a primary effect that was not apparent from genomic data. The data also reveal that T21 results in extensive proteome remodeling similarly affecting proteins encoded by all chromosomes. Finally, we found broad, organelle-specific posttranscriptional effects such as significant down-regulation of the mitochondrial proteome contributing DS hallmarks and variability.

2017-11-01 | PXD004880 | Pride

Transcriptomic analysis of Nicotiana benthamiana plants infected with a plum pox virus (PPV) deletion mutant (P1Pro) that lacks the self-cleavage inhibitory domain of the P1 leader protease

Project description:Transcriptomes of wild-type Nicotiana benthamiana plants inoculated with plum pox virus (PPV) or the P1Pro clone, a PPV deletion mutant that lacks the self-cleavage inhibitory domain of the P1 leader protease; in addition, N. benthamiana nahG-expressing plants inoculated with P1Pro were analyzed to identify genes whose expression is altered by P1Pro infections but does not depend on salicylic acid signaling.

2020-07-30 | GSE146746 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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