ire-1;isp-1

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Genetic mutants with ire-1, isp-1 alterations

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

Lifespan (days)
21.9
Lifespan change (compared to wild type)
8.42%
Phenotype
Inactivation of ire-1 shortened wild-type lifespan by an average of 22% and ire-1 knockdown shortened the extended lifespan caused by the isp-1 mutation by an average of less than 20%.
Lifespan comparisons
Double mutant ire-1(RNAi);isp-1(qm150) has a lifespan of 21.9 days, while single mutant ire-1(RNAi) has a lifespan of 17.4 days, single mutant isp-1(qm150) has a lifespan of 24.2 days and wild type has a lifespan of 20.2 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Lifespan (days)
23.5
Lifespan change (compared to wild type)
16.92%
Phenotype
Inactivation of ire-1 shortened wild-type lifespan by an average of 22% and ire-1 knockdown shortened the extended lifespan caused by the isp-1 mutation by an average of less than 20%.
Lifespan comparisons
Double mutant ire-1(RNAi);isp-1(qm150) has a lifespan of 23.5 days, while single mutant ire-1(RNAi) has a lifespan of 16.6 days, single mutant isp-1(qm150) has a lifespan of 23.4 days and wild type has a lifespan of 20.1 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

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

Lifespan (days)
19.1
Lifespan change (compared to wild type)
28.19%
Phenotype
Inactivation of ire-1 shortened wild-type lifespan by an average of 22% and ire-1 knockdown shortened the extended lifespan caused by the isp-1 mutation by an average of less than 20%.
Lifespan comparisons
Double mutant ire-1(ok799);isp-1(qm150) has a lifespan of 19.1 days, while single mutant ire-1(ok799) has a lifespan of 11.3 days, single mutant isp-1(qm150) has a lifespan of 22.2 days and wild type has a lifespan of 14.9 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Lifespan (days)
21.1
Lifespan change (compared to wild type)
41.61%
Phenotype
Inactivation of ire-1 shortened wild-type lifespan by an average of 22% and ire-1 knockdown shortened the extended lifespan caused by the isp-1 mutation by an average of less than 20%.
Lifespan comparisons
Double mutant ire-1(ok799);isp-1(qm150) has a lifespan of 21.1 days, while single mutant ire-1(ok799) has a lifespan of 11.3 days, single mutant isp-1(qm150) has a lifespan of 22.2 days and wild type has a lifespan of 14.9 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Lifespan (days)
21.8
Lifespan change (compared to wild type)
24.57%
Phenotype
Inactivation of ire-1 shortened wild-type lifespan by an average of 22% and ire-1 knockdown shortened the extended lifespan caused by the isp-1 mutation by an average of less than 20%.
Lifespan comparisons
Double mutant ire-1(ok799);isp-1(qm150) has a lifespan of 21.8 days, while single mutant ire-1(ok799) has a lifespan of 10.9 days, single mutant isp-1(qm150) has a lifespan of 22.3 days and wild type has a lifespan of 17.5 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Search genes: ire-1 isp-1

Entrez ID
Symbol
GenAge
Wormbase ID

174305
ire-1
View on GenAge (ire-1)
WBGene00002147

IRE1 kinase related;Serine/threonine-protein kinase

Locus: CELE_C41C4.4

Wormbase description: ire-1 encodes a transmembrane serine/threonine protein kinase and site-specific endoribonuclease orthologous to Saccharomyces cerevisiae inositol-requiring 1 protein kinase (Ire1) and human endoplasmic reticulum-to-nucleus signaling 1 (ERN1, OMIM:604033); IRE-1 is required for the unfolded protein response (UPR) that counteracts cellular stress induced by accumulation of unfolded proteins in the endoplasmic reticulum (ER); in response to ER stress, IRE-1 cleaves xbp-1 mRNA to produce transcriptionally active XBP-1 that positively regulates UPR gene expression in order to maintain ER homeostasis.

Entrez ID
Symbol
GenAge
Wormbase ID

177609
isp-1
View on GenAge (isp-1)
WBGene00002162

Cytochrome b-c1 complex subunit Rieske, mitochondrial

Locus: CELE_F42G8.12

Wormbase description: isp-1 encodes a Rieske iron sulphur protein (ISP) which is a subunit of the mitochondrial complex III in the mitochondrial membrane; the subunits are highly conserved in all mitochondria and aerobic bacteria; mitochondrial complex III catalyses electron transport from ubiquinol to cytochrome c; isp-1 mutants show low oxygen consumption, a decreased sensitivity to reactive oxygen species and increased lifespan suggesting that mitochondrial electron transport is a key factor affecting life span; isp-1 affects the rates of physiological processes like reproduction and development and also affects behavior.

Orthologs of ire-1;isp-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Ern1;Uqcrfs1
Mus musculus	Ern2;Uqcrfs1
Mus musculus	Uqcrfs1;Ern1
Mus musculus	Uqcrfs1;Ern2

Orthologs of ire-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Ire1
Mus musculus	Ern1
Mus musculus	Ern2

Orthologs of isp-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Uqcrfs1