frh-1;skn-1

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Genetic mutants with frh-1, skn-1 alterations

Names of genes are ordered alphabetically. For the order of interventions, please see the specific paper.

Temperature °C
20
Lifespan (days)
18.75
Lifespan change (compared to wild type)
25.00%
Phenotype
frh-1 RNAi increased lifespan on wild-type strains as well as on skn-1(zu67).
Lifespan comparisons
Double mutant frh-1(RNAi);skn-1(zu67) has a lifespan of 18.75 days, while single mutant frh-1(RNAi) has a lifespan of 21.5 days, single mutant skn-1(zu67) has a lifespan of 11.0 days and wild type has a lifespan of 15.0 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Ventura N et al., 2009, p53/CEP-1 increases or decreases lifespan, depending on level of mitochondrial bioenergetic stress. Aging Cell. 8(4):380-93 19416129 Click here to select all mutants from this PubMed ID in the graph
Abstract
Mitochondrial pathologies underlie a number of life-shortening diseases in humans. In the nematode Caenorhabditis elegans, severely reduced expression of mitochondrial proteins involved in electron transport chain-mediated energy production also leads to pathological phenotypes, including arrested development and/or shorter life; in sharp contrast, mild suppression of these same proteins extends lifespan. In this study, we show that the C. elegans p53 ortholog cep-1 mediates these opposite effects. We found that cep-1 is required to extend longevity in response to mild suppression of several bioenergetically relevant mitochondrial proteins, including frataxin - the protein defective in patients with Friedreich's Ataxia. Importantly, we show that cep-1 also mediates both the developmental arrest and life shortening induced by severe mitochondrial stress. These findings support an evolutionarily conserved function for p53 in modulating organismal responses to mitochondrial dysfunction and suggest that metabolic checkpoint responses may play a role in longevity control and in human mitochondrial-associated diseases.

Temperature °C
20
Lifespan (days)
20.2
Lifespan change (compared to wild type)
27.04%
Phenotype
frh-1 RNAi increased lifespan on wild-type strains as well as on skn-1(zu67).
Lifespan comparisons
Double mutant frh-1(RNAi);skn-1(zu67) has a lifespan of 20.2 days, while single mutant frh-1(RNAi) has a lifespan of 20.4 days, single mutant skn-1(zu67) has a lifespan of 12.3 days and wild type has a lifespan of 15.9 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Ventura N et al., 2009, p53/CEP-1 increases or decreases lifespan, depending on level of mitochondrial bioenergetic stress. Aging Cell. 8(4):380-93 19416129 Click here to select all mutants from this PubMed ID in the graph
Abstract
Mitochondrial pathologies underlie a number of life-shortening diseases in humans. In the nematode Caenorhabditis elegans, severely reduced expression of mitochondrial proteins involved in electron transport chain-mediated energy production also leads to pathological phenotypes, including arrested development and/or shorter life; in sharp contrast, mild suppression of these same proteins extends lifespan. In this study, we show that the C. elegans p53 ortholog cep-1 mediates these opposite effects. We found that cep-1 is required to extend longevity in response to mild suppression of several bioenergetically relevant mitochondrial proteins, including frataxin - the protein defective in patients with Friedreich's Ataxia. Importantly, we show that cep-1 also mediates both the developmental arrest and life shortening induced by severe mitochondrial stress. These findings support an evolutionarily conserved function for p53 in modulating organismal responses to mitochondrial dysfunction and suggest that metabolic checkpoint responses may play a role in longevity control and in human mitochondrial-associated diseases.

Search genes: frh-1 skn-1

Entrez ID
Symbol
GenAge
Wormbase ID

174002
frh-1
View on GenAge (frh-1)
WBGene00001486

Frataxin, mitochondrial

Locus: CELE_F59G1.7

Wormbase description: frh-1 encodes the C. elegans frataxin ortholog; by homology, FRH-1 is predicted to be a mitochondrial protein required for biogenesis of iron-sulfur clusters, co-factors necessary for proper function of electron transport chain proteins; in C. elegans, loss of frh-1 activity via RNAi results in small body size, pale coloration, reduced motility, decreased pharyngeal pumping and defecation, reduced egg-laying and fertility, hypersensitivity to oxidative stress, and altered adult lifespan; an frh-1::gfp promoter fusion is expressed in neurons, the pharynx, gut, spermatheca and body wall muscle; in the pharynx, FRH-1 localizes to the mitochondria.

Entrez ID
Symbol
GenAge
Wormbase ID

177343
skn-1
View on GenAge (skn-1)
WBGene00004804

Protein skinhead-1;SKiNhead

Locus: CELE_T19E7.2

Wormbase description: skn-1 encodes a bZip transcription factor orthologous to the mammalian Nrf (Nuclear factor-erythroid-related factor) transcription factors; during early embryogenesis, maternally provided SKN-1 is required for specification of the EMS blastomere, a mesendodermal precursor that gives rise to pharyngeal, muscle, and intestinal cells; later, during postembryonic development, SKN-1 functions in the p38 MAPK pathway to regulate the oxidative stress response and in parallel to DAF-16/FOXO in the DAF-2-mediated insulin/IGF-1-like signaling pathway to regulate adult lifespan; in vitro assays indicate that SKN-1 can be directly phosphorylated by the AKT-1, AKT-2, and SGK-1 kinases that lie downstream of DAF-2 in the insulin signaling pathway and in vivo experiments suggest that this phosphorylation is essential for regulation of SKN-1 nuclear accumulation and hence, transcriptional regulator activity; in the early embryo, SKN-1 is detected at highest levels in nuclei of the P1 blastomere and its descendants through the 8-cell stage of embryogenesis; later in embryogenesis, SKN-1 is observed in all hypodermal and intestinal nuclei, with reporter constructs indicating that intestinal expression begins as early as the 50-100-cell stage; in larvae and young adults, SKN-1::GFP reporters are expressed in the intestine and ASI neurons, with expression in intestinal nuclei enhanced under conditions of stress or reduced DAF-2 signaling.

Orthologs of frh-1;skn-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Fxn;Nfe2
Mus musculus	Fxn;Nfe2l2
Mus musculus	Fxn;Nfe2l1
Mus musculus	Nfe2;Fxn
Mus musculus	Nfe2l2;Fxn
Mus musculus	Nfe2l1;Fxn

Orthologs of frh-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	fh
Mus musculus	Fxn

Orthologs of skn-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Nfe2
Mus musculus	Nfe2l2
Mus musculus	Nfe2l1