DVE-1_ChIP-seq and HDA-1_ChIP-seq of worms
Ontology highlight
ABSTRACT:
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE141042 | GEO | 2020/07/19
REPOSITORIES: GEO
Similar Datasets
Project description: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.
2020-07-19 | GSE141041 | GEO
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
Project description:DVE-1_ChIP-seq and HDA-1_ChIP-seq of worms
| PRJNA591856 | ENA
Project description:Across eukaryotic species, mild mitochondrial stress can have beneficial effects on the lifespan of organisms. Mitochondrial dysfunction activates an unfolded protein response (UPRmt), a stress signaling mechanism designed to ensure mitochondrial homeostasis. Perturbation of mitochondria during larval development in C. elegans not only delays aging but also maintains UPRmt signaling, suggesting an epigenetic mechanism that modulates both longevity and mitochondrial proteostasis throughout life. Here we identify the conserved histone lysine demethylases jmjd-1.2/PHF8 and jmjd-3.1/JMJD3 as positive regulators of lifespan in response to mitochondrial dysfunction across species. Reduction-of-function of the demethylases potently suppresses longevity and UPRmt induction while gain-of-function is sufficient to extend lifespan in an UPRmt-dependent manner. A systems genetics approach in the BXD mouse reference population further indicated conserved roles of the mammalian orthologs in longevity and UPRmt signaling. These findings illustrate an evolutionary conserved epigenetic mechanism that determines the rate of aging downstream of mitochondrial perturbations.
2016-05-03 | GSE78990 | GEO
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: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
Project description:The special AT-rich sequence-binding (SATB) protein DVE-1 is widely recognized for its pivotal involvement in orchestrating the retrograde mitochondrial unfolded protein response (mitoUPR) in C. elegans. In our study of downstream factors contributing to lifespan extension in sensory ciliary mutants, we find that DVE-1 is crucial for this longevity effect independent of its canonical mitoUPR function. Additionally, DVE-1 also influences lifespan under conditions of dietary restriction and germline loss, again distinct from its role in mitoUPR. Mechanistically, while mitochondrial stress typically prompts nuclear accumulation of DVE-1 to initiate the transcriptional mitoUPR program, these long-lived mutants reduce DVE-1 nuclear accumulation, likely by enhancing its cytosolic translocation. This observation suggests a cytosolic role for DVE-1 in lifespan extension. Overall, our study implies that, in contrast to the more narrowly defined role of the mitoUPR-related transcription factor ATFS-1, DVE-1 may possess broader functions than previously recognized in modulating longevity and defending against stress.
2024-09-27 | GSE276887 | GEO
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
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 2 conditions (untreated, GTPP treatment)
2016-06-28 | E-GEOD-75410 | biostudies-arrayexpress
Project description:Small molecule inhibitors of mitochondrial electron transport chain (ETC) hold significant promise in the field of mitochondrial research and aging biology. In this study, we studied two molecules: mycothiazole (MTZ) - isolated from the marine sponge P. mycofijiensis and its semisynthetic acetylated derivative 8-O-acetylmycothiazole (8-OAc) as efficient alternatives for their high efficiency to inhibit ETC complex I function. Similar to rotenone, a widely used complex I inhibitor, these two compounds showed anticancer activity and strikingly demonstrate a lack of toxicity to non-cancer cells, a highly beneficial feature in the development of anti-cancer therapeutics. Furthermore, experiments with these small molecules in vivo utilizing C.elegans demonstrate their additional utilization to aging studies. We observed that both molecules have the ability to induce a mitochondria-specific unfolded protein response (UPRMT) pathway, which extends lifespan of worms when applied in their adult stage. Interestingly, we also found that these two molecules employ different pathways to extend lifespan in worms, where MTZ utilize the transcription factors, ATFS-1 and HSF-1, which are involved in the UPRMT and heat shock response (HSR) pathways, respectively. In opposition,8-OAc only required HSF-1 and not ATFS-1. This observation elucidates an important insight into the functional roles of various protein subunits of ETC complexes and their regulatory mechanisms associated with aging.
2024-01-01 | E-MTAB-13546 | biostudies-arrayexpress