Transcriptome analysis upon C6orf203 silencing
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE123683 | GEO | 2019/06/13
REPOSITORIES: GEO
Similar Datasets
Project description:The aim of this project was to search for the new factors engaged in mitochondrial nucleic acids metabolism under stress conditions. To this end we treated human 293 cells with mitochondrial replication/transcription inhibitor ethidium bromide and we compared proteomes of untreated vs treated cells. We were looking for the proteins whose level would be differentially regulated in response to disturbed mitochondrial gene expression. In our studies we utilized a stable 293 cell line that inducible expresses a fusion of EGFP with mitochondria targeting sequence. This approach enabled us to control mitochondrial import by analysis of the abundance of mitochondrial EGFP marker. We isolated highly purified mitochondria from the cells, lysed them and subjected protein extracts to labelling with iTRAQ reagents. We performed quantitative analysis of stress- induced changes of human mitochondrial proteome with the use of MaxQuant software.
2019-06-13 | PXD012055 | Pride
Project description:Stress response pathways detect and alleviate many adverse conditions to safeguard cell and tissue homeostasis, yet their prolonged activation induces apoptosis and disrupts organismal health. How stress responses are turned off at the right time and place remains poorly understood. Here, we report a ubiquitin-dependent mechanism to silence the cellular response to mitochondrial protein import stress. Critical to this process is the silencing factor of the integrated stress response (SIFI), a large E3 ligase complex mutated in ataxia that degrades both unimported mitochondrial precursors and stress response components. By recognizing bifunctional substrate motifs that equally encode protein localization and stability, the SIFI complex can rapidly turn off a general stress response after a specific stress has been resolved. Pharmacological stress response silencing sustains cell survival even if stress resolution failed, which underscores the importance of signal termination and provides a roadmap for treating neurodegenerative diseases caused bymitochondrial import defects.
2023-11-22 | GSE232191 | GEO
Project description:DallePazze2014 - Cellular senescene-induced
mitochondrial dysfunction
This model is described in the article:
Dynamic modelling of
pathways to cellular senescence reveals strategies for targeted
interventions.
Dalle Pezze P, Nelson G, Otten EG,
Korolchuk VI, Kirkwood TB, von Zglinicki T, Shanley DP.
PLoS Comput. Biol. 2014 Aug; 10(8):
e1003728
Abstract:
Cellular senescence, a state of irreversible cell cycle
arrest, is thought to help protect an organism from cancer, yet
also contributes to ageing. The changes which occur in
senescence are controlled by networks of multiple signalling
and feedback pathways at the cellular level, and the interplay
between these is difficult to predict and understand. To
unravel the intrinsic challenges of understanding such a highly
networked system, we have taken a systems biology approach to
cellular senescence. We report a detailed analysis of
senescence signalling via DNA damage, insulin-TOR, FoxO3a
transcription factors, oxidative stress response, mitochondrial
regulation and mitophagy. We show in silico and in vitro that
inhibition of reactive oxygen species can prevent loss of
mitochondrial membrane potential, whilst inhibition of mTOR
shows a partial rescue of mitochondrial mass changes during
establishment of senescence. Dual inhibition of ROS and mTOR in
vitro confirmed computational model predictions that it was
possible to further reduce senescence-induced mitochondrial
dysfunction and DNA double-strand breaks. However, these
interventions were unable to abrogate the senescence-induced
mitochondrial dysfunction completely, and we identified
decreased mitochondrial fission as the potential driving force
for increased mitochondrial mass via prevention of mitophagy.
Dynamic sensitivity analysis of the model showed the network
stabilised at a new late state of cellular senescence. This was
characterised by poor network sensitivity, high signalling
noise, low cellular energy, high inflammation and permanent
cell cycle arrest suggesting an unsatisfactory outcome for
treatments aiming to delay or reverse cellular senescence at
late time points. Combinatorial targeted interventions are
therefore possible for intervening in the cellular pathway to
senescence, but in the cases identified here, are only capable
of delaying senescence onset.
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2024-09-02 | BIOMD0000000582 | BioModels
Project description:Defects in mitochondrial metabolism have been increasingly linked with age-onset protein misfolding diseases such as Alzheimerâs, Parkinsonâs, and Huntingtonâs. In response to protein folding stress, compartment-specific unfolded protein responses (UPRs) within the endoplasmic reticulum, mitochondria, and cytosol work in parallel to ensure cellular protein homeostasis. While perturbation of individual compartments can make other compartments more susceptible to protein stress, the cellular conditions that trigger cross-communication between the individual UPRs remain poorly understood. We have uncovered a conserved, robust mechanism linking mitochondrial protein homeostasis and the cytosolic folding environment through changes in lipid homeostasis. Metabolic restructuring caused by mitochondrial stress or small molecule activators trigger changes in gene expression coordinated uniquely by both the mitochondrial and cytosolic UPRs, protecting the cell from disease-associated proteins. Our data suggest an intricate and unique system of communication between UPRs in response to metabolic changes that could unveil new targets for diseases of protein misfolding. Because the induction of the MCSR due to hsp-6 RNAi required both hsf-1 and dve-1, key transcription factors required for the HSR and UPRmt, respectively, we asked which gene sets are coordinately regulated by both factors. We performed microarray analyses to determine which genes have their expression altered by hsp-6 RNAi and whether these genes are regulated either by hsf-1, dve-1 or both
2016-09-08 | E-GEOD-83722 | biostudies-arrayexpress
Project description:Pelleted non-perturbed LNCaP cells were lysed using LysisBuffer (8 M urea, 0.1 M ammonium bicarbonate, 0.1 % RapiGest) and nucleic acids sheared using sonication.
2018-01-22 | MSV000081956 | MassIVE
Project description:Defects in mitochondrial metabolism have been increasingly linked with age-onset protein misfolding diseases such as Alzheimer’s, Parkinson’s, and Huntington’s. In response to protein folding stress, compartment-specific unfolded protein responses (UPRs) within the endoplasmic reticulum, mitochondria, and cytosol work in parallel to ensure cellular protein homeostasis. While perturbation of individual compartments can make other compartments more susceptible to protein stress, the cellular conditions that trigger cross-communication between the individual UPRs remain poorly understood. We have uncovered a conserved, robust mechanism linking mitochondrial protein homeostasis and the cytosolic folding environment through changes in lipid homeostasis. Metabolic restructuring caused by mitochondrial stress or small molecule activators trigger changes in gene expression coordinated uniquely by both the mitochondrial and cytosolic UPRs, protecting the cell from disease-associated proteins. Our data suggest an intricate and unique system of communication between UPRs in response to metabolic changes that could unveil new targets for diseases of protein misfolding.
2016-09-08 | GSE83722 | GEO
Project description:Eukaryotic cells are constantly challenged by the presence of reactive oxygen species, which play an important role in aging and human disease progression. In particular, acute oxidative stress can lead to extensive damage to cellular DNA, proteins, and lipids and can trigger a response that remodels the transcriptional and translational state of the cell. Although a number of previous studies have profiled the relative changes in mRNA and protein and more studies revealing the dynamics of transcription and translation in response to stress are starting to emerge, a quantitative view of this response has been lacking. Here, we have applied quantitative methods to characterize the time dynamics of mRNA and protein levels in the oxidative stress response of the fission yeast Schizosaccharomyces pombe, which has allowed us to perform dynamic modeling of responsive genes in units of copies per cell. Analysis of the resulting time dynamics provided a new genome-wide view of the scale, timing and rates of transcription and translation in the transient response. The majority of dynamic genes were observed to be responsive in their mRNA or protein levels alone implying extensive translational regulation. Nevertheless, modeling of genes with responsive mRNA and protein levels showed that protein levels could, in a majority of these cases, be accurately predicted with constant translation and decay rates while a minority benefited from explicit translation delay parameters. A number of independent features, e.g. measures of codon bias, ribosome occupancy, etc., were found to be less correlated to maximally perturbed protein levels than steady-state levels. Codon bias measures were more correlated than mRNA levels to quantitative protein levels at both perturbed and un-perturbed states. Measures of translation activity, on the other hand, were only significantly correlated at steady state. In total 32 samples: 11 for stressed time series R1, 11 for stressed time series R2, 5 for control time series C1 and 5 for control time series C2
2015-03-01 | E-GEOD-62120 | biostudies-arrayexpress
Project description:Shutoff of global protein synthesis is a conserved response to cellular stresses. This general phenomenon is accompanied by induction of distinct gene programs tailored to each stress condition. Although the mechanisms that lead to general repression of protein synthesis are well characterized, how cells reprogram the translation machinery for selective gene expression remains poorly understood. Here we show that the noncanonical 5′ cap-binding protein eIF3d is specifically activated in response to metabolic stress, due to loss of CK2-mediated phosphorylation near the eIF3d cap-binding pocket. Activated eIF3d controls a gene program enriched in factors important for glucose homeostasis, including members of the mTOR pathway, and eIF3d-mediated translation adaptation is essential for cell survival during chronic glucose deprivation. Our findings reveal a new mechanism of translation reprogramming engaged in response to metabolic stress.
2020-11-16 | GSE158249 | GEO
Project description:Searching for stress inducible architectural noncoding RNAs
| PRJDB12380 | ENA
Project description:Searching for stress inducible architectural noncoding RNAs
| PRJDB12381 | ENA