Metabolic determinants of cellular fitness dependent on mitochondrial reactive oxygen species
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA663327 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12638000.fastq.gz | Fastqsanger.gz | |||
| SRR12638001.fastq.gz | Fastqsanger.gz | |||
| SRR12638002.fastq.gz | Fastqsanger.gz | |||
| SRR12638003.fastq.gz | Fastqsanger.gz | |||
| SRR12638004.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 192 |
Similar Datasets
Project description:Mitochondria-derived reactive oxygen species (mROS) are required for the survival, proliferation, and metastasis of cancer cells. The mechanism by which mitochondrial metabolism regulates mROS levels to support cancer cells is not fully understood. To address this, we conducted a metabolism-focused CRISPR/Cas9 genetic screen and uncovered that loss of genes encoding subunits of mitochondrial complex I were deleterious in the presence of the mitochondria-targeted antioxidant Mito-Vitamin E (MVE). Genetic or pharmacologic inhibition of mitochondrial complex I in combination with the mitochondria-targeted antioxidants, MVE or MitoTEMPO, induced a robust integrated stress response (ISR) and markedly diminished cell survival and proliferation in vitro. Notably, this was not observed following inhibition of mitochondrial complex III. Administration of MitoTEMPO in combination with the mitochondrial complex I inhibitor phenformin decreased the leukemic burden in a mouse model of T-cell acute lymphoblastic leukemia. Thus, mitochondrial complex I is a dominant metabolic determinant of mROS-dependent cellular fitness.
2020-09-15 | GSE157912 | GEO
Project description:Mitochondria-derived reactive oxygen species (mROS) are required for the survival, proliferation, and metastasis of cancer cells. The mechanism by which mitochondrial metabolism regulates mROS levels to support cancer cells is not fully understood. To address this, we conducted a metabolism-focused CRISPR-Cas9 genetic screen and uncovered that loss of genes encoding subunits of mitochondrial complex I was deleterious in the presence of the mitochondria-targeted antioxidant mito-vitamin E (MVE). Genetic or pharmacologic inhibition of mitochondrial complex I in combination with the mitochondria-targeted antioxidants, MVE or MitoTEMPO, induced a robust integrated stress response (ISR) and markedly diminished cell survival and proliferation in vitro. This was not observed following inhibition of mitochondrial complex III. Administration of MitoTEMPO in combination with the mitochondrial complex I inhibitor phenformin decreased the leukemic burden in a mouse model of T cell acute lymphoblastic leukemia. Thus, mitochondrial complex I is a dominant metabolic determinant of mROS-dependent cellular fitness.
| S-EPMC7673681 | biostudies-literature
Project description:mitochondrial electron transport in Arabidopsis leaves was blocked by antimycin A treatment to trigger mitochondrial production of reactive oxygen species and to study transcriptional changes in response
2010-12-31 | E-TABM-641 | biostudies-arrayexpress
Project description:While reactive oxygen species (ROS) have long been known to drive aging and neurodegenera-tion, their persistent depletion below basal levels also disrupts organismal function. Cells counter-act loss of basal ROS via the reductive stress response, but the identity and biochemical activity of ROS sensed by this pathway remain unknown. Here, we show that the reductive stress E3 ligase CUL2FEM1B specifically acts at mitochondrial TOM complexes, where it is regulated by ROS that are produced as byproducts of complex III of the electron transport chain (ETC) during oxidative phosphorylation. By modulating localized CUL2FEM1B activity, ROS tune protein import into mitochondria and thereby control the abundance of the rate-limiting ETC complex IV. As complex III yields most ROS when the ETC outpaces metabolic demands or oxygen availability, our findings identify basal ROS as sentinels of mitochondrial activity that help cells adjust their ETC to fluctuating environments, as required for cell differentiation and survival.
2024-12-05 | PXD057954 | Pride
Project description:Cellular membrane proteins are a critical part of the host defense mechanisms against infection and intracellular survival of Listeria monocytogenes. The complex spatiotemporal regulation of bacterial infection by various membrane proteins has been challenging to study. Here, using mass spectrometry analyses, we depicted the dynamic expression landscape of membrane proteins upon L. monocytogenes infection in dendritic cells. We showed that Dynein light chain 1 (Dynll1) formed a persistent complex with the mitochondrial cytochrome oxidase, Cox4i1 that is disturbed by pathogen insult. We discovered that the dissociation of the Dynll1-Cox4i1 complex is required for the release of mitochondrial reactive oxygen species and serves as a regulator of intracellular proliferation of Listeria monocytogenes. Our study shows that Dynll1 is an inhibitor of mitochondrial reactive oxygen species and can serve as a potential molecular drug target for antibacterial treatment.
2020-02-17 | PXD016452 |
Project description:In this study, we investigated the impact of PZH on inducing reactive oxygen species (ROS) to inhibit colorectal cancer (CRC) growth. CRC cell line HCT116 was exposed to PZH for 24 hours, then RNA-Sequencing was conducted and showed that PZH modulated ROS-related signaling pathways, including DNA repair and the unfolded protein response, concomitant with the suppression of proliferation-related genes such as PCNA and Ki-67.
2023-10-19 | GSE245680 | GEO
Project description:We were interested in investigating the transcriptome responses to exogenous applications of brassinosteroid hormone when Arabidopsis seedlings are pre-stressed with a reactive oxygen species, hydrogen peroxide. We were interested in seeing which subsets of BR-responsive gene transcripts were most affected and how BR-responsive gene transcripts responded to increasing concentrations of hydrogen peroxide both as a whole and individually.
2011-02-28 | GSE20756 | GEO
Project description:Wollbold2014 - Effects of reactive oxygen
species
This model is described in the article:
Anti-inflammatory effects of
reactive oxygen species ¿ a multi-valued logical model
validated by formal concept analysis.
Wollbold J, Jaster R, Müller S,
Rateitschak K, Wolkenhauer O.
BMC Syst Biol 2014 Sep; 8(1): 101
Abstract:
BackgroundRecent findings suggest that in pancreatic acinar
cells stimulated with bile acid, a pro-apoptotic effect of
reactive oxygen species (ROS) dominates their effect on
necrosis and spreading of inflammation. The first effect
presumably occurs via cytochrome C release from the inner
mitochondrial membrane. A pro-necrotic effect ¿ similar to
the one of Ca2+ ¿ can be strong opening of mitochondrial
pores leading to breakdown of the membrane potential, ATP
depletion, sustained Ca2+ increase and premature activation of
digestive enzymes. To explain published data and to understand
ROS effects during the onset of acute pancreatitis, a model
using multi-valued logic is constructed. Formal concept
analysis (FCA) is used to validate the model against data as
well as to analyze and visualize rules that capture the
dynamics.ResultsSimulations for two different levels of bile
stimulation and for inhibition or addition of antioxidants
reproduce the qualitative behaviour shown in the experiments.
Based on reported differences of ROS production and of ROS
induced pore opening, the model predicts a more uniform
apoptosis/necrosis ratio for higher and lower bile stimulation
in liver cells than in pancreatic acinar cells. FCA confirms
that essential dynamical features of the data are captured by
the model. For instance, high necrosis always occurs together
with at least a medium level of apoptosis. At the same time,
FCA helps to reveal subtle differences between data and
simulations. The FCA visualization underlines the protective
role of ROS against necrosis.ConclusionsThe analysis of the
model demonstrates how ROS and decreased antioxidant levels
contribute to apoptosis. Studying the induction of necrosis via
a sustained Ca2+ increase, we implemented the commonly accepted
hypothesis of ATP depletion after strong bile stimulation.
Using an alternative model, we demonstrate that this process is
not necessary to generate the dynamics of the measured
variables. Opening of plasma membrane channels could also lead
to a prolonged increase of Ca2+ and to necrosis. Finally, the
analysis of the model suggests a direct experimental testing
for the model-based hypothesis of a self-enhancing cycle of
cytochrome C release and ROS production by interruption of the
mitochondrial electron transport chain.
This model is hosted on
BioModels Database
and identified by:
MODEL1407230001.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2015-04-15 | MODEL1407230001 | BioModels
Project description:Renal Proximal Tubular Cells of young / senescent replicative age or high / low reactive oxygen species content were profiled using an Affymetrix Chip Platform.<br>Sample classifications: <br>Young refers to the in vitro age of early passage cells. <br>Senescent indicates cells at the end of their in vitro life span, having entered an irreversible growth arrest. <br>SortHI refers to cells with high intracellular reactive oxygen species content that were sorted by FACS according to a bright FL1 fluorescence after staining with 1 ï¾µM CM-H2DCFDA (Molecular Probes Cat No C6827).<br>SortLO refers to cells with low intracellular reactive oxygen species content that were sorted by FACS according to a dim FL1 fluorescence after staining with 1 ï¾µM CM-H2DCFDA.<br>
2011-01-15 | E-MEXP-2683 | biostudies-arrayexpress
Project description:We were interested in investigating the transcriptome responses to exogenous applications of brassinosteroid hormone when Arabidopsis seedlings are pre-stressed with a reactive oxygen species, hydrogen peroxide. We were interested in seeing which subsets of BR-responsive gene transcripts were most affected and how BR-responsive gene transcripts responded to increasing concentrations of hydrogen peroxide both as a whole and individually. Liquid culture Arabidopsis seedlings are grown under standard conditions. Hydrogen peroxide is added at various concentrations to pre-stress the seedlings. Following this pretreatment, the seedlings are then treated with brassinosteroid (BR) hormone (epi-brassinolide, BL). Following this treatment, seedlings are harvested and total RNA is extracted for genome-wide transcriptome analysis.
2011-02-28 | E-GEOD-20756 | biostudies-arrayexpress