ACONITASE 3 is post-translationally controlled in response to mitochondrial stress signals in Arabidopsis
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive HF
ORGANISM(S): Arabidopsis Thaliana (mouse-ear Cress)
TISSUE(S): Leaf
SUBMITTER: 
Jesús Pascual
LAB HEAD: Saijaliisa Kangasjärvi
PROVIDER: PXD024316 | Pride | 2021-06-08
REPOSITORIES: Pride
Similar Datasets
Project description:We characterized the global response of plants carrying a mitochondrial dysfunction induced by the expression of the unedited form of the ATP synthase 9 subunit. The u-ATP9 transgene driven by A9 and Apetala3 promoters induce mitochondrial dysfunction revealed by a decrease in both oxygen uptake and ATP levels, with an increase in ROS and a concomitant oxidative stress response. The transcriptome analysis of young Arabidopsis flowers, validated by RT-PCR and enzymatic or functional tests, show dramatic changes in u-ATP9 plants. Both lines present a modification in the expression of several genes involved in carbon, lipid and cell wall metabolism, suggesting that an important metabolic readjustment occurs in plants with a mitochondrial dysfunction. Interestingly, transcript levels involved in mitochondrial biogenesis, protein synthesis, and degradation are affected. Moreover, several mRNA levels for transcription factors and DNA binding proteins were also changed. Some of them are involved in stress and hormone response, suggesting that several signaling pathways overlap. Indeed, the transcriptome data reveal that the mitochondrial dysfunction dramatically alters genes involved in signaling pathways, including those involved in ethylene, absicic acid and auxin signal transduction. Our data suggest that the mitochondrial dysfunction model used in this rapport may be useful to uncover the retrograde signaling mechanism between the nucleus and mitochondria in plant cells. Arabidopsis oligonucleotide microarrays fabricated by the University of Arizona contain 26,000 oligonucleotides (http://www.ag.arizona.edu/microarray/). RNA was isolated from 6-week-old flowers from u-ATP9 and wt plants. The experimental (mutant) and reference (wild type) RNA samples were reverse-transcribed and directly labeled with either Cy5-dUTP or Cy3-dUTP fluorescent dye (GE Healthcare), using random hexamer primers (Invitrogen). Excess nucleotides and primers were removed using QIAquick PCR Purification Kit (Qiagen). Labeled samples were mixed and then hybridized to microarray for 15 h at 60°C. The slides were washed at room temperature in three wash steps: 2 x SSC, 0.5% SDS; 0.5 x SSC; and 0.05 x SSC for 5 min each with gentle shaking. The slides were scanned with a GenePix 4000B Scanner (Axon Instruments Inc., Union City, CA). Normalization between the Cy3 and Cy5 fluorescent dye emission channels was achieved by adjusting the levels of both image intensities. The experiments were repeated four times with samples from different experiments, as biological replicates. In dye swapping experiments, the RNA samples from different experiments were reciprocally labeled, both as a biological and technical repetition for comparing the reproducibility of the experiments. Hybridization intensities for each microarray element were measured using ScanAlyze 4.24 (available at http://genome-www4.stanford.edu/MicroArray/SMD/restech.html). The two channels were normalized in log space using the z-score normalization on a 95% trimmed data set. We removed unreliable spots according to the following criteria: spots flagged as having false intensity caused by dust or background on the array were removed; and spots for which intensity was less than three fold above background were also eliminated. Data from multiple experiments were normalized (Bolstad, 2003) and signals from spots from different experiments were statistically analyzed using Significance Analysis of Microarrays using the one class response (SAM, http://www-stat.stanford.edu/~tibs/SAM/), cut at a false discovery rate < 10% (Tusher, 2001).
2009-02-15 | E-GEOD-14240 | biostudies-arrayexpress
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.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000582.
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.
2015-08-12 | BIOMD0000000582 | BioModels
Project description:Mitochondria are tightly embedded within metabolic and regulatory networks that optimize plant performance in response to environmental challenges. The best-known mitochondrial retrograde signaling pathway involves stress-induced activation of the transcription factor NAC DOMAIN CONTAINING PROTEIN 17 (ANAC017), which initiates protective responses to stress-induced mitochondrial dysfunction in Arabidopsis (Arabidopsis thaliana). Post-translational control of the elicited responses, however, remains poorly understood. Previous studies linked protein phosphatase 2A subunit PP2A-B’γ, a key negative regulator of stress responses, with reversible phosphorylation of ACONITASE 3 (ACO3). Here we report on ACO3 and its phosphorylation at Ser91 as key components of stress regulation that are induced by mitochondrial dysfunction. Targeted mass spectrometry-based proteomics revealed that the abundance and phosphorylation of ACO3 increased under stress, which required signaling through ANAC017. Phosphomimetic mutation at ACO3-Ser91 and accumulation of ACO3S91D-YFP promoted the expression of genes related to mitochondrial dysfunction. Furthermore, ACO3 contributed to plant tolerance against UV-B or antimycin A-induced mitochondrial dysfunction. These findings demonstrate that ACO3 is both a target and mediator of mitochondrial dysfunction signaling, and critical for achieving stress tolerance in Arabidopsis leaves.
2022-03-14 | PXD018881 | panorama
Project description:Hexadecenal, a trans (-2,3-) unsaturated fatty aldehyde, is an intermediate of the sphingolipid degradation pathway. This pathway, induced during cellular stress, involves the conversion of sphingosine-1-phosphate to hexadecenal by Sphingosine-1-Phosphate-Lyase (SPL) in humans and DPL1 in yeast. Hexadecenal is further metabolized to hexadecenoic acid by Fatty Aldehyde Dehydrogenase (ALDH3A2 in humans and HFD1 in yeast). Trans-2-hexadecenal (t-2-hex), has been found to induce mitochondrial dysfunction in a conserved manner from yeast to humans. However, the specific mechanisms and biological targets underlying this lipid-induced mitochondrial inhibition remain largely unknown. In this study, we employed unbiased transcriptomic approaches using the Saccharomyces cerevisiae yeast model to elucidate the principal mechanisms and biological targets associated with t-2-hex-induced mitochondrial dysfunction. To investigate the effects of t-2-hex, we utilized an hfd1 mutant strain lacking the HFD1 gene. This strain exhibited increased sensitivity to t-2-hex treatment compared to wild-type cells. Exponentially growing hfd1 mutant cells were exposed to 100 μM t-2-hex for a duration of 3 hours, while control cells were incubated with the solvent dimethyl sulfoxide (DMSO), in which hexadecenal is dissolved. Total RNA was extracted from both treated and control cells for high-throughput sequencing analysis. Through transcriptomic profiling, we aimed to identify differentially expressed genes, pathways, and regulatory networks associated with t-2-hex-induced mitochondrial dysfunction in yeast. This study provides a comprehensive analysis of the transcriptional response to t-2-hex treatment, shedding light on the molecular mechanisms and potential biological targets underlying lipid-induced mitochondrial dysfunction.
2023-07-31 | E-MTAB-13188 | biostudies-arrayexpress
Project description:Autophagy mitigates ethanol-induced mitochondrial dysfunction and oxidative stress in esophageal keratinocytes
| PRJNA600739 | ENA
Project description:Metabolic dysfunction associated steatotic liver disease (MASLD) is characterized by a constant accumulation of lipids in the liver. This lipotoxicity in the liver is associated with dysregulation of the first step in lipid catabolism called beta oxidation in the mitochondrial matrix, eventually leading to mitochondrial dysfunction. To evaluate possible involvement of mitochondrial DNA methylation in this lipid metabolic dysfunction we investigated the functional metabolic effects of mitochondrial overexpression of CpG (MSssI) and GpC (MCviPI) DNA methyltransferases in relation to gene expression and (mito)epigenetic signatures. Overall, the results show that mitochondrial GpC and to a lesser extent CpG methylation increase bile acid metabolic gene expression, inducing cholestasis by mito-nuclear epigenetic reprogramming. Moreover, increased expression of metabolic nuclear receptors in both MSssI and MCviPI cells promote mitochondrial swelling and induce basal overactivation of mitochondrial respiration which favours lipid accumulation and metabolic-stress induced mitophagy and autophagy stress responses. Altogether GpC and CpG mitochondrial induce a metabolic challenging environment that is similar to mitochondrial dysfunction in the progression of MASLD.
2023-12-08 | GSE241526 | GEO
Project description:Metabolic dysfunction associated steatotic liver disease (MASLD) is characterized by a constant accumulation of lipids in the liver. This lipotoxicity in the liver is associated with dysregulation of the first step in lipid catabolism called beta oxidation in the mitochondrial matrix, eventually leading to mitochondrial dysfunction. To evaluate possible involvement of mitochondrial DNA methylation in this lipid metabolic dysfunction we investigated the functional metabolic effects of mitochondrial overexpression of CpG (MSssI) and GpC (MCviPI) DNA methyltransferases in relation to gene expression and (mito)epigenetic signatures. Overall, the results show that mitochondrial GpC and to a lesser extent CpG methylation increase bile acid metabolic gene expression, inducing cholestasis by mito-nuclear epigenetic reprogramming. Moreover, increased expression of metabolic nuclear receptors in both MSssI and MCviPI cells promote mitochondrial swelling and induce basal overactivation of mitochondrial respiration which favours lipid accumulation and metabolic-stress induced mitophagy and autophagy stress responses. Altogether GpC and CpG mitochondrial induce a metabolic challenging environment that is similar to mitochondrial dysfunction in the progression of MASLD.
2023-12-08 | GSE240988 | GEO
Project description:Mitochondrial integrated stress response emerged as a major adaptive pathway to respiratory chain deficiency, but tissue-specifics of its regulation or how it adapts to different levels of mitochondrial dysfunction are largely unknown. Here we report that diverse levels of mitochondrial cardiomyopathy activate mitoISR, including high production of FGF21, a cytokine with both paracrine and endocrine function, shown to be induced by respiratory chain dysfunction. Remarkably, although being fully dispensable for the cell-autonomous and systemic responses to severe mitochondrial cardiomyopathy, in the conditions of mild-to-moderate cardiac OXPHOS dysfunction, FGF21 regulates a portion of the mitoISR. In the absence of FGF21, a large part of the metabolic adaptation to mitochondrial dysfunction (one-carbon metabolism, transsulfuration and serine and proline biosynthesis) is strongly blunted, independent of the primary mitoISR activator ATF4. Collectively, our work highlights the complexity of mitochondrial stress responses by revealing the importance of the tissue-specificity and dose-dependency of the mitoISR.
2022-02-04 | GSE195947 | GEO
Project description:Chronic obstructive pulmonary disease (COPD) is a heterogenous respiratory disease mainly caused by smoking. Respiratory infections constitute a major risk factor for acute worsening of COPD symptoms or COPD exacerbation. Mitochondrial functionality, which is crucial for the execution of physiologic functions of metabolically active cells, is impaired in airway epithelial cells (AECs) of COPD patients as well as smokers. However, the potential contribution of mitochondrial dysfunction in AECs to progression of COPD, infection-triggered exacerbations in AECs and a potential mechanistic link between mitochondrial and epithelial barrier dysfunction is unknown to date. In this study, we used an in vitro COPD exacerbation model based on AECs exposed to cigarette smoke extract (CSE) followed by infection with Streptococcus pneumoniae (Sp). The levels of oxidative stress, as an indicator of mitochondrial stress were quantified upon CSE and Sp. The expression of proteins associated with mitophagy, mitochondrial content and biogenesis as well as mitochondrial fission and fusion was quantified upon CSE and Sp. Transcriptional AEC profiling was performed to identify the potential changes in innate immune pathways and correlate them with mitochondrial function. We found that CSE exposure substantially altered mitochondrial function in AECs by suppressing mitochondrial complex protein levels, reducing mitochondrial membrane potential and increasing mitochondrial stress and mitophagy. Moreover, CSE-induced mitochondrial dysfunction correlated with reduced enrichment of genes involved in apical junctions and innate immune responses to Sp, particularly type I interferon responses. Together, our results demonstrated that CSE-induced mitochondrial dysfunction may contribute to impaired innate immune responses to Sp and may thus trigger COPD exacerbation.
2022-05-27 | GSE197751 | GEO
Project description:Akt-Induced Mitochondrial Dysfunction in the Heart
| PRJNA269253 | ENA