ftn-1;ftn-2;gas-1

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Genetic mutants with ftn-1, ftn-2, gas-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)
14.85
Lifespan change (compared to wild type)
-33.73%
Phenotype
Depleting ftn-1/2 did not rescue the shortened lifespan of the gas-1 mutant
Lifespan comparisons
Triple mutant ftn-1(RNAi);ftn-2(RNAi);gas-1(fc21) has a lifespan of 14.85 days, while double mutant ftn-1(RNAi);ftn-2(RNAi) has a lifespan of 22.0 days, single mutant gas-1(fc21) has a lifespan of 15.28 days and wild type has a lifespan of 22.41 days.
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: ftn-1 ftn-2 gas-1 ftn-1;ftn-2;gas-1

Entrez ID
Symbol
GenAge
Wormbase ID

179138
ftn-1
View on GenAge (ftn-1)
WBGene00001500

Ferritin

Locus: CELE_C54F6.14

Wormbase description: ftn-1 encodes one of two C. elegans ferritin heavy chain homologs; ftn-1 activity is essential for normal lifespan under iron stress conditions and, in addition, has been reported to be essential for embryogenesis; an ftn-1::gfp reporter is expressed in the intestine at all stages of development and its expression, as well as that of ftn-1 mRNA, increases under iron stress conditions and in the background of mutations in the second ferritin-encoding gene, ftn-2.

Entrez ID
Symbol
GenAge
Wormbase ID

171934
ftn-2
View on GenAge (ftn-2)
WBGene00001501

Ferritin

Locus: CELE_D1037.3

Wormbase description: ftn-2 encodes one of two C. elegans ferritin heavy chain homologs; loss of ftn-2 activity via deletion mutation results in slightly lower brood sizes and, under iron stress conditions, slightly faster growth from the L4 to adult stage of development, and slightly reduced lifespan; an ftn-2::gfp reporter fusion is expressed in diverse tissues, including the pharynx, intestine, and hypodermis, and its expression, along with that of ftn-2 mRNA, does not appear to change significantly under iron stress conditions.

Entrez ID
Symbol
GenAge
Wormbase ID

181646
gas-1
View on GenAge (gas-1)
WBGene00001520

Probable NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial

Locus: CELE_K09A9.5

Wormbase description: The gas-1 gene encodes a 49 kDa subunit of mitochondrial complex I that is required for oxidative phosphorylation, resistance to volatile anesthetics, fecundity, and normal lifespan; gas-1 is expressed in the nematode neuromuscular system; its subcellular distribution appears to be mitochondrial; drug effects on mutants versus wild-type indicate that gas-1 functions at least partially through presynaptic effects; gas-1 mutants have strongly reduced Complex I-dependent metabolism in mitochondria, while Complex II-dependent metabolism is conversely increased in mutants; gas-1 mitochondria look structurally normal.

Orthologs of ftn-1;ftn-2;gas-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Fer3HCH;Fer3HCH;ND-49
Mus musculus	Fth1;Fth1;Ndufs2
Mus musculus	Fth1;Ftmt;Ndufs2
Mus musculus	Ftmt;Ftmt;Ndufs2

Orthologs of ftn-1 in SynergyAge

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Species	Gene

Orthologs of ftn-2 in SynergyAge

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Species	Gene

Orthologs of gas-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	ND-49
Mus musculus	Ndufs2