Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

FNDC-1-Mediated Mitophagy and ATFS-1 Coordinate to Protect Against Hypoxia-Reoxygenation

ABSTRACT: Mitochondrial Quality Control (MQC) balances organelle adaptation and elimination, and mechanistic crosstalk between the underlying molecular processes impacts subsequent stress outcomes. FUN14 Domain Containing 1 (FUNDC1) is a mammalian mitophagy receptor that responds to hypoxia-reoxygenation (HR) stress. Here, we provide evidence that FNDC-1 is the C. elegans ortholog of FUNDC1, and that its loss protects against injury in a worm model of HR. This protection depends upon ATFS-1, a transcription factor that is central to the mitochondrial unfolded protein response (UPRmt). Global mRNA and metabolite profiling suggest that atfs-1 dependent stress responses and metabolic remodeling occur in response to the loss of fndc-1. These data support a role for FNDC-1 in non-hypoxic MQC, and further suggest that these changes are prophylactic in relation to subsequent HR. Our results highlight functional coordination between mitochondrial adaptation and elimination that organizes stress responses and metabolic rewiring to protect against HR injury.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE158628 | GEO | 2021/09/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

V-ATPase/TORC1-mediated ATFS-1 translation directs mitochondrial UPR activation in C. elegans

Project description:To adapt mitochondrial function to the ever-changing intra- and extra-cellular environment, multiple mitochondrial stress response (MSR) pathways, including the mitochondrial unfolded protein response (UPRmt), have evolved. However, how the mitochondrial stress signal is sensed and relayed to UPRmt transcription factors, such as ATFS-1 in Caenorhabditis elegans, remains largely unknown. Here, we show that a panel of vacuolar H+-ATPase (v-ATPase) subunits and the target of rapamycin complex 1 (TORC1) activity are essential for the cytosolic relay of mitochondrial stress to ATFS-1, and for the induction of the UPRmt. Mechanistically, mitochondrial stress stimulates v-ATPase/Rheb-dependent TORC1 activation, subsequently promoting ATFS-1 translation. Increased translation of ATFS-1 upon mitochondrial stress furthermore relies on a set of ribosomal components, but is independent of GCN-2/PEK-1 signaling. Finally, the v-ATPase and ribosomal subunits are required for mitochondrial surveillance and mitochondrial stress-induced longevity. These results reveal a v-ATPase-TORC1-ATFS-1 signaling pathway that links mitochondrial stress to the UPRmt through intimate crosstalks between multiple organelles.

2022-09-23 | GSE179517 | GEO

ATFS-1 mediates a protective transcription program during mitochondrial stress

Project description:ATFS-1 has been shown to regulate transcription of mitochondrial chaperone genes such as mtHsp70/hsp-6 and hsp-60 in response to mitocondrial stress. To identify the entire ATFS-1-mediated response, we compared the transcript profiles from wild-type and atfs-1(tm4525) worms raised in the absence and presence of mitochondrial stress. We used microarrays to identify genes regulated by ATFS-1 during mitochondrial stress RNA samples were prepared from wild-type(wt) and atfs-1(tm4525)(mutant) worms fed either control(RNAi) or spg-7(RNAi). Worms were synchronized by bleaching, raised in liquid culture and harvested at the L4 stage. Control is denoted as C and spg-7 treatment is denoted T. Each experiment was performed in triplicate indicated as 1,2 and 3.

2012-07-11 | E-GEOD-38196 | biostudies-arrayexpress

ATFS-1 mediates a protective transcription program during mitochondrial stress

2012-07-12 | GSE38196 | GEO

ATFS-1 regulates a broad protective transcriptional program

Project description:We previously identified a number of genes which were differentially expressed during mitochondrial stress in an ATFS-1-dependent manner using an atfs-1 loss-of-function mutant allele . To complement the findings from our previous microarray, we compared the transcript profiles from wild-type and atfs-1(et18) gain-of-function worms (which have constitutively active ATFS-1) in the absence of mitochondrial stress. We used microarrays to identify genes regulated by ATFS-1 using a gain-of-function allele of atfs-1.

2016-03-21 | GSE73669 | GEO

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. Wildtype worms treated spg-7(RNAi) are analyzed in the presence and absence of ATFS-1 antibody to identify ATFS-1 targets. Individual samples were analyzed. Wildtype worms treated spg-7(RNAi) in the absence of antibody is used as a control.

2015-03-03 | E-GEOD-63803 | biostudies-arrayexpress

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

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 | GSE148328 | GEO

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

2020-12-07 | GSE156830 | 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

Role of mitochondrial unfolded protein response transcription fatcor ATFS-1 in lifespan of long-lived mitochondrial mutants

Project description:In this work, we examined the effect of the transcription factor ATFS-1 in the long lifespan of the nuo-6 mitochondrial mutant. We also examined the effect of the hypoxia transcription factor hif-1. We sequenced both atfs-1 deletion mutants and atfs-1 gain-of-function point mutants in which the mitochondrial localization sequence of ATFS-1 is disrupted. Note that sequencing batch 2 was previously uploaded as part of GSE93724.

2018-11-21 | GSE110984 | GEO

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