Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hsf3 governs intramitochondrial ROS homeostasis via regulating respiratory process [ChIP-Seq]

ABSTRACT: Mitochondrial quality control is essential in modulating intramitochondrial ROS (mtROS) homeostasis that is a critical determinant for many human disorders. Here we identified an atypical function of a heat shock factor, Hsf3, as an important mtROS regulator. Despite HSFs are nuclear proteins and master regulators of protein unfolded response (UPR) across taxa, we demonstrate that Hsf3 is a both nuclei and mitochondria targeting transcription factor that plays an irrelevant function in controlling UPR process. Instead, Hsf3 represses TCA cycle genes and simultaneously regulates electron transfer chain genes encoded from both nuclei and mitochondria. Moreover, both nuclear and mitochondrial targeting signal are required for promising Hsf3 function. Hsf3 regulation responds to multiple intramitochondrial stresses, which activates and ameliorates Hsf3 DNA binding via oxidation of the cysteine residue on DNA binding domain of Hsf3. Collectively, our findings reveal a previously unknown role of HSF family in modulation of mitochondrial function and damage.

ORGANISM(S): Cryptococcus neoformans var. grubii H99

PROVIDER: GSE183183 | GEO | 2021/09/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Cryptococcus neoformans Hsf3 LC-MS/MS

Project description:Mitochondrial quality control is essential in modulating intramitochondrial ROS (mtROS) homeostasis that is a critical determinant for many human disorders. Here we identified an atypical function of a heat shock factor, Hsf3, as an important mtROS regulator. Despite HSFs are nuclear proteins and master regulators of protein unfolded response (UPR) across taxa, we demonstrate that Hsf3 is a both nuclei and mitochondria targeting transcription factor that plays an irrelevant function in controlling UPR process. Instead, Hsf3 represses TCA cycle genes and simultaneously regulates electron transfer chain genes encoded from both nuclei and mitochondria. Moreover, both nuclear and mitochondrial targeting signal are required for promising Hsf3 function. Hsf3 regulation responds to multiple intramitochondrial stresses, which activates and ameliorates Hsf3 DNA binding via oxidation of the cysteine residue on DNA binding domain of Hsf3. Collectively, our findings reveal a previously unknown role of HSF family in modulation of mitochondrial function and damage.

2022-09-01 | PXD033799 | Pride

Hsf3 governs intramitochondrial ROS homeostasis via regulating respiratory process [RNA-Seq]

2021-09-20 | GSE183182 | GEO

Mitohormesis reprograms macrophage metabolism to enforce tolerance [BMDM_tolerance_RNAseq]

Project description:Macrophages generate mitochondrial reactive oxygen and electrophilic species (mtROS, mtRES) as antimicrobials during Toll-like receptor (TLR)-dependent inflammatory responses. Whether mitochondrial stress caused by these molecules impacts macrophage function is unknown. Here, we demonstrate that both pharmacologically- and lipopolysaccharide (LPS)-driven mitochondrial stress in macrophages triggers a stress response called mitohormesis. LPS-driven mitohormetic stress adaptations occur as macrophages transition from an LPS-responsive to LPS-tolerant state where stimulus-induced proinflammatory gene transcription is impaired, suggesting tolerance is a product of mitohormesis. Indeed, like LPS, hydroxyestrogen-triggered mitohormesis suppresses mitochondrial oxidative metabolism and acetyl-CoA production needed for histone acetylation and proinflammatory gene transcription, and is sufficient to enforce an LPS-tolerant state. Thus, mtROS and mtRES are TLR-dependent signaling molecules that trigger mitohormesis as a negative feedback mechanism to restrain inflammation via tolerance. Moreover, bypassing TLR signaling and pharmacologically triggering mitohormesis represents a novel anti-inflammatory strategy that co-opts this stress response to impair epigenetic support of proinflammatory gene transcription by mitochondria.

2021-04-04 | GSE169730 | GEO

Mitohormesis reprograms macrophage metabolism to enforce tolerance [BMDM_ChIPseq]

2021-04-04 | GSE169729 | GEO

Mitohormesis reprograms macrophage metabolism to enforce tolerance [vWAT_mac_RNAseq]

2021-04-04 | GSE169728 | GEO

Mitohormesis reprograms macrophage metabolism to enforce tolerance [BMDM_OHestrogen_RNAseq]

2021-04-04 | GSE169727 | GEO

Gene expression profiles between mtROShigh and mtROSlow cells dissociated from E14.5 neocortical cells were compared by microarray

Project description:sample collection protocol:We used FACS to separate the E14.5 neocortical cells into high mitochondrial reactive oxygen species (mtROS) and low mitochondrial ROS cell populations and compared their expression profiles. Transition of progenitors through progressive stages of differentiation probably involves dynamic changes in mtROS levels, depending on the needs of the cell. We found that the progenitors had higher levels of mtROS, but these levels significantly decreased with differentiation.

2017-03-30 | E-MTAB-5438 | biostudies-arrayexpress

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

To identify ATFS-1 target genes during mitochondrial stress

Project description:To better understand genome coordination and OXPHOS recovery during mitochondrial dysfunction, we examined ATFS-1, a transcription factor that regulates mitochondria-to nuclear communication during the mitochondrial UPR, via ChIP-sequencing.

2015-03-03 | GSE63803 | GEO

Investigating impacts of mycothiazole and its synthetic derivative on mitochondrial function and aging in C. elegans

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data