Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MRNA-seq of worms and the mitochondrial unfolded protein response (UPRmt)

ABSTRACT: To cope with a challenging and unpredictable environment, living systems have evolved several organelle-specific stress responses, e.g. the cytosolic heat shock response (HSR), the endoplasmic reticulum unfolded protein response (UPRER) and the mitochondrial unfolded protein response (UPRmt). UPRmt monitors mitochondrial function and homeostasis in general. However, the mechanism of UPRmt remains largely unexplored. Here we identified that histone deacetylase HDA-1 is associated with homeobox domain-containing protein DVE-1 in UPRmt activation in Caenorhabditis elegans. Knocking down ATP synthase subunit atp-2 generates mitochondrial stress and induces UPRmt. After analyzing the mRNA profiles of worms on L4440 RNAi, hda-1 RNAi or dve-1 RNAi and untreated or treated with atp-2 RNAi, we found that 283 hda-1_dependent genes and 218 dve-1_dependent genes were upregulated in response to atp-2 RNAi.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE141041 | GEO | 2020/07/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

DVE-1_ChIP-seq and HDA-1_ChIP-seq of worms

Project description:Mitochondria are important organelles, but their function is often challenged by toxic products of metabolism as well as by pathogen attack. The mitochondrial unfolded protein response (UPRmt) monitors mitochondrial function in general: it is responsible for buffering the mitochondrial protein folding environment, and controlling mitochondria-nuclear balance of the electron transport chain (ETC) components. Besides, UPRmt plays essential roles in aging and lifespan. Here we found that knocking down histone deacetylase hda-1 robustly attenuated UPRmt and lifespan extension. We identified HDA-1 as a required factor for UPRmt activation and HDA-1 is associated with the homeobox domain-containing protein DVE-1.So, we performed ChIP-seq of worms to find DNA regions on which HDA-1 and DVE-1 bound, and if their binding depend on each other.

2020-07-19 | GSE141042 | GEO

mRNA-seq of worms who raised on control RNAi or prp-19 RNAi were untreated or treated with atp-2 RNAi

Project description:Mitochondria are the central hub of energy and metabolism of the cell,acting as one of the most important organelles of living cells.Under mitochondrial stresses, cells will trigger mitochondrial unfolded protein response (UPRmt) to maintain mitochondrial homeostasis.We have verified that splicing facotrs are required for the activation of UPRmt.Knocking down of splicing fator prp-19 could supresse UPRmt activation.We analysis the differencial alternative splicing of worms on L4440 RNAi or prp-19 RNAi and untreated or treated with atp-2 RNAi, we found that inhibition of prp-19 interrupts splicing homeostasis of c.elegans.

2022-12-31 | GSE191294 | GEO

Lipid biosynthesis coordinates a Mitochondrial to Cytosolic Stress Response

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

The nucleosome remodeling and deacetylase (NuRD) complex mediates the mitochondrial unfolded protein response and longevity in C. elegans

Project description:Mitochondrial stress during development causes widespread changes in chromatin structure to promote mitochondrial unfolded protein response (UPRmt), perpetuating an early response across a lifetime results in lifespan extension. We found that the nucleosome remodeling and deacetylase (NuRD) complex interact with the transcription factor DVE-1 to initiate the global chromatin condensation and induce the UPRmt in animals experienced with mild mitochondrial dysfunction. The condensed chromatin structure can be well maintained into later life that is beneficial for lifespan extension. Moreover, overexpression of the core component of the NuRD complex is sufficient to induce the UPRmt response and longevity in C. elegans. Thus, a transient mitochondrial stress response during early development is established and propagated into later life through the NuRD-dependent chromatin remodeling pathway to extend lifespan.

2020-07-31 | GSE143904 | GEO

Mitochondrial unfolded protein response controls matrix pre-RNA processing and translation

Project description:The mitochondrial matrix is unique in that it must integrate folding and assembly of proteins derived from nuclear and mitochondrial genomes. In C. elegans, the mitochondrial unfolded protein response (UPRmt) senses matrix protein misfolding and induces a program of nuclear gene expression, including mitochondrial chaperonins, to promote mitochondrial proteostasis. While misfolded mitochondrial matrix-localized ornithine trans-carbamylase (OTC) induces chaperonin expression, our understanding of mammalian UPRmt is rudimentary, reflecting a lack of acute triggers for UPRmt activation. This limitation has prevented analysis of the cellular responses to matrix protein misfolding and the effects of UPRmt on mitochondrial translation to control protein folding loads. Here, we combine pharmacological inhibitors of matrix-localized HSP90/TRAP1 or LON protease, which promote chaperonin expression, with global transcriptional and proteomic analysis to reveal an extensive and acute response of human cells to UPRmt. This response involved widespread induction of nuclear genes, including matrix-localized proteins involved in folding, pre-RNA processing and translation. Functional studies revealed rapid but reversible translation inhibition in mitochondria occurring concurrently with defects in pre-RNA processing due to transcriptional repression and LON-dependent turnover of the mitochondrial pre-RNA processing nuclease MRPP3. This study reveals that acute mitochondrial protein folding stress activates both increased chaperone availability within the matrix and reduced matrix-localized protein synthesis through translational inhibition, and provides a framework for further dissection of mammalian UPRmt. triplicate experiment of 3 conditions (untreated, GTPP treatment, CDDO treatment)

2016-06-28 | E-GEOD-75247 | biostudies-arrayexpress

Mitochondrial unfolded protein response controls matrix pre-RNA processing and translation

2016-06-28 | E-GEOD-75410 | biostudies-arrayexpress

The transcriptional coactivator CBP/p300 is an evolutionarily conserved node that promotes longevity in response to mitochondrial stress [HepG2]

Project description:Organisms respond to mitochondrial stress by activating multiple defense pathways including the mitochondrial unfolded protein response (UPRmt). However, how different layers of UPRmt regulators are orchestrated to transcriptionally activate the stress responses remains largely unknown. Here we identified CBP-1, the worm ortholog of the mammalian acetyltransferases CBP/p300, as an essential regulator for UPRmt activation, as well as for mitochondrial stress-induced immune response, amyloid-β aggregation reduction and lifespan extension in Caenorhabditis elegans. Mechanistically, CBP-1 acts downstream of histone demethylases, JMJD-1.2/JMJD-3.1, and upstream of UPRmt transcription factors including ATFS-1, to systematically induce a broad spectrum of UPRmt genes and execute multiple beneficial functions. In mouse and human populations, transcript levels of CBP/p300 positively correlate with UPRmt transcripts and longevity. Furthermore, CBP/p300 inhibition disrupts, while forced expression of p300 is sufficient to activate, the UPRmt in mammalian cells. These results highlight an evolutionarily conserved mechanism that determines mitochondrial stress response, and promotes health and longevity through CBP/p300.

2020-12-07 | GSE156830 | GEO

The transcriptional coactivator CBP/p300 is an evolutionarily conserved node that promotes longevity in response to mitochondrial stress [ChIP-seq]

2020-12-07 | GSE148328 | GEO

The transcriptional coactivator CBP/p300 is an evolutionarily conserved node that promotes longevity in response to mitochondrial stress [Mus musculus]

2020-12-07 | GSE131613 | GEO

The transcriptional coactivator CBP/p300 is an evolutionarily conserved node that promotes longevity in response to mitochondrial stress [C. elegans]

2020-12-07 | GSE131611 | GEO