cep-1;frh-1

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Genetic mutants with cep-1, frh-1 alterations

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

Temperature °C
20
Lifespan (days)
20.0
Lifespan change (compared to wild type)
33.33%
Phenotype
cep-1(gk138) significantly shortened the increase in lifespan induced by frh-1 RNAi.
Lifespan comparisons
Double mutant cep-1(gk138);frh-1(RNAi) has a lifespan of 20.0 days, while single mutant frh-1(RNAi) has a lifespan of 25.0 days, single mutant cep-1(gk138) has a lifespan of 17.66 days and wild type has a lifespan of 15.0 days.
Type of interaction
See methods
Dependent
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: cep-1 frh-1

Entrez ID
Symbol
GenAge
Wormbase ID

172616
cep-1
View on GenAge (cep-1)
WBGene00000467

Transcription factor cep-1

Locus: CELE_F52B5.5

Wormbase description: cep-1 encodes an ortholog of the human tumor suppressor p53 (OMIM:191170, mutated in Li-Fraumeni syndrome) that promotes DNA damage-induced apoptosis and is required for normal meiotic segregation in the germ line, and affects sensitivity to hypoxia-induced lethality and longevity in response to starvation; CEP-1 is expressed ubiquitously in embryos and in the nucleoli of a subset of pharyngeal cells.

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.

Orthologs of cep-1;frh-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of cep-1 in SynergyAge

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Species	Gene

Orthologs of frh-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	fh
Mus musculus	Fxn

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SynergyAge database hosts high-quality, manually curated information about the synergistic and antagonistic lifespan effects of genetic interventions in model organisms, also allowing users to explore the longevity relationships between genes in a visual way.