cep-1;clk-1

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Genetic mutants with cep-1, clk-1 alterations

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

Temperature °C
20
Diet
OP50
Lifespan (days)
14.44
Lifespan change (compared to wild type)
-15.06%
Phenotype
The cep-1;clk-1 double mutant lived as long as the clk-1 single mutant
Lifespan comparisons
Double mutant cep-1(gk138);clk-1(e2519) has a lifespan of 14.44 days, while single mutant clk-1(e2519) has a lifespan of 21.0 days and wild type has a lifespan of 17.0 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Baruah A et al., 2014, CEP-1, the Caenorhabditis elegans p53 homolog, mediates opposing longevity outcomes in mitochondrial electron transport chain mutants. PLoS Genet. 10(2):e1004097 24586177 Click here to select all mutants from this PubMed ID in the graph
Abstract
Caenorhabditis elegans CEP-1 and its mammalian homolog p53 are critical for responding to diverse stress signals. In this study, we found that cep-1 inactivation suppressed the prolonged lifespan of electron transport chain (ETC) mutants, such as isp-1 and nuo-6, but rescued the shortened lifespan of other ETC mutants, such as mev-1 and gas-1. We compared the CEP-1-regulated transcriptional profiles of the long-lived isp-1 and the short-lived mev-1 mutants and, to our surprise, found that CEP-1 regulated largely similar sets of target genes in the two mutants despite exerting opposing effects on their longevity. Further analyses identified a small subset of CEP-1-regulated genes that displayed distinct expression changes between the isp-1 and mev-1 mutants. Interestingly, this small group of differentially regulated genes are enriched for the "aging" Gene Ontology term, consistent with the hypothesis that they might be particularly important for mediating the distinct longevity effects of CEP-1 in isp-1 and mev-1 mutants. We further focused on one of these differentially regulated genes, ftn-1, which encodes ferritin in C. elegans, and demonstrated that it specifically contributed to the extended lifespan of isp-1 mutant worms but did not affect the mev-1 mutant lifespan. We propose that CEP-1 responds to different mitochondrial ETC stress by mounting distinct compensatory responses accordingly to modulate animal physiology and longevity. Our findings provide insights into how mammalian p53 might respond to distinct mitochondrial stressors to influence cellular and organismal responses.

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

Temperature °C
20
Diet
OP50
Lifespan (days)
25.88
Lifespan change (compared to wild type)
15.33%
Phenotype
cep-1 mutation does not suppress clk-1 mutant longevity as the lifespans of two cep-1;clk-1 double mutant isolates (L4, L6) are similar to that of the clk-1 single mutant. Mutation in cep-1;clk-1L4
Lifespan comparisons
Double mutant cep-1(gk138);clk-1(qm150) has a lifespan of 25.88 days, while single mutant clk-1(qm150) has a lifespan of 26.1 days, single mutant cep-1(gk138) has a lifespan of 21.36 days and wild type has a lifespan of 22.44 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Baruah A et al., 2014, CEP-1, the Caenorhabditis elegans p53 homolog, mediates opposing longevity outcomes in mitochondrial electron transport chain mutants. PLoS Genet. 10(2):e1004097 24586177 Click here to select all mutants from this PubMed ID in the graph
Abstract
Caenorhabditis elegans CEP-1 and its mammalian homolog p53 are critical for responding to diverse stress signals. In this study, we found that cep-1 inactivation suppressed the prolonged lifespan of electron transport chain (ETC) mutants, such as isp-1 and nuo-6, but rescued the shortened lifespan of other ETC mutants, such as mev-1 and gas-1. We compared the CEP-1-regulated transcriptional profiles of the long-lived isp-1 and the short-lived mev-1 mutants and, to our surprise, found that CEP-1 regulated largely similar sets of target genes in the two mutants despite exerting opposing effects on their longevity. Further analyses identified a small subset of CEP-1-regulated genes that displayed distinct expression changes between the isp-1 and mev-1 mutants. Interestingly, this small group of differentially regulated genes are enriched for the "aging" Gene Ontology term, consistent with the hypothesis that they might be particularly important for mediating the distinct longevity effects of CEP-1 in isp-1 and mev-1 mutants. We further focused on one of these differentially regulated genes, ftn-1, which encodes ferritin in C. elegans, and demonstrated that it specifically contributed to the extended lifespan of isp-1 mutant worms but did not affect the mev-1 mutant lifespan. We propose that CEP-1 responds to different mitochondrial ETC stress by mounting distinct compensatory responses accordingly to modulate animal physiology and longevity. Our findings provide insights into how mammalian p53 might respond to distinct mitochondrial stressors to influence cellular and organismal responses.

Temperature °C
20
Diet
OP50
Lifespan (days)
26.52
Lifespan change (compared to wild type)
18.18%
Phenotype
cep-1 mutation does not suppress clk-1 mutant longevity as the lifespans of two cep-1;clk-1 double mutant isolates (L4, L6) are similar to that of the clk-1 single mutant. Mutation in cep-1;clk-1L6
Lifespan comparisons
Double mutant cep-1(gk138);clk-1(qm150) has a lifespan of 26.52 days, while single mutant clk-1(qm150) has a lifespan of 26.1 days, single mutant cep-1(gk138) has a lifespan of 21.36 days and wild type has a lifespan of 22.44 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Baruah A et al., 2014, CEP-1, the Caenorhabditis elegans p53 homolog, mediates opposing longevity outcomes in mitochondrial electron transport chain mutants. PLoS Genet. 10(2):e1004097 24586177 Click here to select all mutants from this PubMed ID in the graph
Abstract
Caenorhabditis elegans CEP-1 and its mammalian homolog p53 are critical for responding to diverse stress signals. In this study, we found that cep-1 inactivation suppressed the prolonged lifespan of electron transport chain (ETC) mutants, such as isp-1 and nuo-6, but rescued the shortened lifespan of other ETC mutants, such as mev-1 and gas-1. We compared the CEP-1-regulated transcriptional profiles of the long-lived isp-1 and the short-lived mev-1 mutants and, to our surprise, found that CEP-1 regulated largely similar sets of target genes in the two mutants despite exerting opposing effects on their longevity. Further analyses identified a small subset of CEP-1-regulated genes that displayed distinct expression changes between the isp-1 and mev-1 mutants. Interestingly, this small group of differentially regulated genes are enriched for the "aging" Gene Ontology term, consistent with the hypothesis that they might be particularly important for mediating the distinct longevity effects of CEP-1 in isp-1 and mev-1 mutants. We further focused on one of these differentially regulated genes, ftn-1, which encodes ferritin in C. elegans, and demonstrated that it specifically contributed to the extended lifespan of isp-1 mutant worms but did not affect the mev-1 mutant lifespan. We propose that CEP-1 responds to different mitochondrial ETC stress by mounting distinct compensatory responses accordingly to modulate animal physiology and longevity. Our findings provide insights into how mammalian p53 might respond to distinct mitochondrial stressors to influence cellular and organismal responses.

Temperature °C
20
Diet
OP50
Lifespan (days)
23.81
Lifespan change (compared to wild type)
8.77%
Phenotype
cep-1 mutation does not suppress clk-1 mutant longevity as the lifespans of two cep-1;clk-1 double mutant isolates (L4, L6) are similar to that of the clk-1 single mutant. Mutation in cep-1;clk-1LN4
Lifespan comparisons
Double mutant cep-1(gk138);clk-1(qm150) has a lifespan of 23.81 days, while single mutant clk-1(qm150) has a lifespan of 25.09 days, single mutant cep-1(gk138) has a lifespan of 19.81 days and wild type has a lifespan of 21.89 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Baruah A et al., 2014, CEP-1, the Caenorhabditis elegans p53 homolog, mediates opposing longevity outcomes in mitochondrial electron transport chain mutants. PLoS Genet. 10(2):e1004097 24586177 Click here to select all mutants from this PubMed ID in the graph
Abstract
Caenorhabditis elegans CEP-1 and its mammalian homolog p53 are critical for responding to diverse stress signals. In this study, we found that cep-1 inactivation suppressed the prolonged lifespan of electron transport chain (ETC) mutants, such as isp-1 and nuo-6, but rescued the shortened lifespan of other ETC mutants, such as mev-1 and gas-1. We compared the CEP-1-regulated transcriptional profiles of the long-lived isp-1 and the short-lived mev-1 mutants and, to our surprise, found that CEP-1 regulated largely similar sets of target genes in the two mutants despite exerting opposing effects on their longevity. Further analyses identified a small subset of CEP-1-regulated genes that displayed distinct expression changes between the isp-1 and mev-1 mutants. Interestingly, this small group of differentially regulated genes are enriched for the "aging" Gene Ontology term, consistent with the hypothesis that they might be particularly important for mediating the distinct longevity effects of CEP-1 in isp-1 and mev-1 mutants. We further focused on one of these differentially regulated genes, ftn-1, which encodes ferritin in C. elegans, and demonstrated that it specifically contributed to the extended lifespan of isp-1 mutant worms but did not affect the mev-1 mutant lifespan. We propose that CEP-1 responds to different mitochondrial ETC stress by mounting distinct compensatory responses accordingly to modulate animal physiology and longevity. Our findings provide insights into how mammalian p53 might respond to distinct mitochondrial stressors to influence cellular and organismal responses.

Temperature °C
20
Diet
OP50
Lifespan (days)
25.77
Lifespan change (compared to wild type)
17.72%
Phenotype
cep-1 mutation does not suppress clk-1 mutant longevity as the lifespans of two cep-1;clk-1 double mutant isolates (L4, L6) are similar to that of the clk-1 single mutant. Mutation in cep-1;clk-1LN6
Lifespan comparisons
Double mutant cep-1(gk138);clk-1(qm150) has a lifespan of 25.77 days, while single mutant clk-1(qm150) has a lifespan of 25.09 days, single mutant cep-1(gk138) has a lifespan of 19.81 days and wild type has a lifespan of 21.89 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Baruah A et al., 2014, CEP-1, the Caenorhabditis elegans p53 homolog, mediates opposing longevity outcomes in mitochondrial electron transport chain mutants. PLoS Genet. 10(2):e1004097 24586177 Click here to select all mutants from this PubMed ID in the graph
Abstract
Caenorhabditis elegans CEP-1 and its mammalian homolog p53 are critical for responding to diverse stress signals. In this study, we found that cep-1 inactivation suppressed the prolonged lifespan of electron transport chain (ETC) mutants, such as isp-1 and nuo-6, but rescued the shortened lifespan of other ETC mutants, such as mev-1 and gas-1. We compared the CEP-1-regulated transcriptional profiles of the long-lived isp-1 and the short-lived mev-1 mutants and, to our surprise, found that CEP-1 regulated largely similar sets of target genes in the two mutants despite exerting opposing effects on their longevity. Further analyses identified a small subset of CEP-1-regulated genes that displayed distinct expression changes between the isp-1 and mev-1 mutants. Interestingly, this small group of differentially regulated genes are enriched for the "aging" Gene Ontology term, consistent with the hypothesis that they might be particularly important for mediating the distinct longevity effects of CEP-1 in isp-1 and mev-1 mutants. We further focused on one of these differentially regulated genes, ftn-1, which encodes ferritin in C. elegans, and demonstrated that it specifically contributed to the extended lifespan of isp-1 mutant worms but did not affect the mev-1 mutant lifespan. We propose that CEP-1 responds to different mitochondrial ETC stress by mounting distinct compensatory responses accordingly to modulate animal physiology and longevity. Our findings provide insights into how mammalian p53 might respond to distinct mitochondrial stressors to influence cellular and organismal responses.

Search genes: cep-1 clk-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

175729
clk-1
View on GenAge (clk-1)
WBGene00000536

5-demethoxyubiquinone hydroxylase, mitochondrial

Locus: CELE_ZC395.2

Wormbase description: clk-1 encodes the C. elegans ortholog of COQ7/CAT5, a highly conserved demethoxyubiquinone (DMQ) hydroxylase that is necessary for the biosynthesis of ubiquinone (coenzyme Q, Q9) from 5-demethoxyubiquinone (DMQ9); in C. elegans, CLK-1 activity is required for normal physiological rates of growth, development, behavior, and aging, as well as for normal brood sizes.

Orthologs of cep-1;clk-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of cep-1 in SynergyAge

Show in SynergyAge
Species	Gene

Orthologs of clk-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	COQ7
Mus musculus	Coq7