egl-1;isp-1

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Genetic mutants with egl-1, isp-1 alterations

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

Temperature °C
20
Lifespan (days)
26.0
Lifespan change (compared to wild type)
69.93%
Phenotype
The longevity caused by the isp(qm150) mutants was not affected by egl-9 RNAi treatment, which significantly increased lifespan of wild type.
Lifespan comparisons
Double mutant egl-1(RNAi);isp-1(qm150) has a lifespan of 26.0 days, while single mutant egl-1(RNAi) has a lifespan of 17.1 days, single mutant isp-1(qm150) has a lifespan of 25.7 days and wild type has a lifespan of 15.3 days.
Type of interaction
See methods
Almost additive (positive)
Citation
View abstract
Lee SJ et al., 2010, Inhibition of respiration extends C. elegans life span via reactive oxygen species that increase HIF-1 activity. Curr Biol. 20(23):2131-6 21093262 Click here to select all mutants from this PubMed ID in the graph
Abstract
A mild inhibition of mitochondrial respiration extends the life span of many organisms, including yeast, worms, flies, and mice, but the underlying mechanism is unknown. One environmental condition that reduces rates of respiration is hypoxia (low oxygen). Thus, it is possible that mechanisms that sense oxygen play a role in the longevity response to reduced respiration. The hypoxia-inducible factor HIF-1 is a highly conserved transcription factor that activates genes that promote survival during hypoxia. In this study, we show that inhibition of respiration in C. elegans can promote longevity by activating HIF-1. Through genome-wide screening, we found that RNA interference (RNAi) knockdown of many genes encoding respiratory-chain components induced hif-1-dependent transcription. Moreover, HIF-1 was required for the extended life spans of clk-1 and isp-1 mutants, which have reduced rates of respiration. Inhibiting respiration appears to activate HIF-1 by elevating the level of reactive oxygen species (ROS). We found that ROS are increased in respiration mutants and that mild increases in ROS can stimulate HIF-1 to activate gene expression and promote longevity. In this way, HIF-1 appears to link respiratory stress in the mitochondria to a nuclear transcriptional response that promotes longevity.

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

Temperature °C
20
Diet
OP50
Lifespan (days)
31.74
Lifespan change (compared to wild type)
61.28%
Phenotype
There were no reduction in ATP levels after heat stress in egl-1;isp-1 double mutants compared to nuo-6.
Lifespan comparisons
Double mutant egl-1(n1084n3082);isp-1(qm150) has a lifespan of 31.74 days, while single mutant isp-1(qm150) has a lifespan of 30.66 days, single mutant egl-1(n1084n3082) has a lifespan of 19.16 days and wild type has a lifespan of 19.68 days.
Type of interaction
See methods
Enhancer, opposite lifespan effects
Citation
View abstract
Yee C et al., 2014, The intrinsic apoptosis pathway mediates the pro-longevity response to mitochondrial ROS in C. elegans. Cell. 157(4):897-909 24813612 Click here to select all mutants from this PubMed ID in the graph
Abstract
The increased longevity of the C. elegans electron transport chain mutants isp-1 and nuo-6 is mediated by mitochondrial ROS (mtROS) signaling. Here we show that the mtROS signal is relayed by the conserved, mitochondria-associated, intrinsic apoptosis signaling pathway (CED-9/Bcl2, CED-4/Apaf1, and CED-3/Casp9) triggered by CED-13, an alternative BH3-only protein. Activation of the pathway by an elevation of mtROS does not affect apoptosis but protects from the consequences of mitochondrial dysfunction by triggering a unique pattern of gene expression that modulates stress sensitivity and promotes survival. In vertebrates, mtROS induce apoptosis through the intrinsic pathway to protect from severely damaged cells. Our observations in nematodes demonstrate that sensing of mtROS by the apoptotic pathway can, independently of apoptosis, elicit protective mechanisms that keep the organism alive under stressful conditions. This results in extended longevity when mtROS generation is inappropriately elevated. These findings clarify the relationships between mitochondria, ROS, apoptosis, and aging.

Temperature °C
20
Diet
OP50
Lifespan (days)
30.48
Lifespan change (compared to wild type)
59.75%
Phenotype
There were no reduction in ATP levels after heat stress in egl-1;isp-1 double mutants compared to nuo-6.
Lifespan comparisons
Double mutant egl-1(n1084n3082);isp-1(qm150) has a lifespan of 30.48 days, while single mutant isp-1(qm150) has a lifespan of 33.78 days, single mutant egl-1(n1084n3082) has a lifespan of 19.1 days and wild type has a lifespan of 19.08 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Yee C et al., 2014, The intrinsic apoptosis pathway mediates the pro-longevity response to mitochondrial ROS in C. elegans. Cell. 157(4):897-909 24813612 Click here to select all mutants from this PubMed ID in the graph
Abstract
The increased longevity of the C. elegans electron transport chain mutants isp-1 and nuo-6 is mediated by mitochondrial ROS (mtROS) signaling. Here we show that the mtROS signal is relayed by the conserved, mitochondria-associated, intrinsic apoptosis signaling pathway (CED-9/Bcl2, CED-4/Apaf1, and CED-3/Casp9) triggered by CED-13, an alternative BH3-only protein. Activation of the pathway by an elevation of mtROS does not affect apoptosis but protects from the consequences of mitochondrial dysfunction by triggering a unique pattern of gene expression that modulates stress sensitivity and promotes survival. In vertebrates, mtROS induce apoptosis through the intrinsic pathway to protect from severely damaged cells. Our observations in nematodes demonstrate that sensing of mtROS by the apoptotic pathway can, independently of apoptosis, elicit protective mechanisms that keep the organism alive under stressful conditions. This results in extended longevity when mtROS generation is inappropriately elevated. These findings clarify the relationships between mitochondria, ROS, apoptosis, and aging.

Temperature °C
20
Diet
OP50
Lifespan (days)
31.72
Lifespan change (compared to wild type)
59.24%
Phenotype
There were no reduction in ATP levels after heat stress in egl-1;isp-1 double mutants compared to nuo-6.
Lifespan comparisons
Double mutant egl-1(n1084n3082);isp-1(qm150) has a lifespan of 31.72 days, while single mutant isp-1(qm150) has a lifespan of 33.92 days, single mutant egl-1(n1084n3082) has a lifespan of 18.96 days and wild type has a lifespan of 19.92 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Yee C et al., 2014, The intrinsic apoptosis pathway mediates the pro-longevity response to mitochondrial ROS in C. elegans. Cell. 157(4):897-909 24813612 Click here to select all mutants from this PubMed ID in the graph
Abstract
The increased longevity of the C. elegans electron transport chain mutants isp-1 and nuo-6 is mediated by mitochondrial ROS (mtROS) signaling. Here we show that the mtROS signal is relayed by the conserved, mitochondria-associated, intrinsic apoptosis signaling pathway (CED-9/Bcl2, CED-4/Apaf1, and CED-3/Casp9) triggered by CED-13, an alternative BH3-only protein. Activation of the pathway by an elevation of mtROS does not affect apoptosis but protects from the consequences of mitochondrial dysfunction by triggering a unique pattern of gene expression that modulates stress sensitivity and promotes survival. In vertebrates, mtROS induce apoptosis through the intrinsic pathway to protect from severely damaged cells. Our observations in nematodes demonstrate that sensing of mtROS by the apoptotic pathway can, independently of apoptosis, elicit protective mechanisms that keep the organism alive under stressful conditions. This results in extended longevity when mtROS generation is inappropriately elevated. These findings clarify the relationships between mitochondria, ROS, apoptosis, and aging.

Search genes: egl-1 isp-1

Entrez ID
Symbol
GenAge
Wormbase ID

179943
egl-1
View on GenAge (egl-1)
WBGene00001170

Programmed cell death activator egl-1

Locus: CELE_F23B12.9

Wormbase description: egl-1 encodes a novel protein that contains a region similar to the BH3 (Bcl-2 homology region 3) domain of mammalian cell death activators; EGL-1 functions as an upstream activator in the general programmed cell death pathway and positively regulates programmed cell death by interacting directly with CED-9 to induce CED-4 release from CED-4/CED-9 complexes and ultimately activate the CED-3 caspase; EGL-1 also induces WAH-1/apoptosis-inducing factor release from the mitochondria; in hermaphrodites, egl-1 is transcriptionally repressed by TRA-1, permitting survival of the HSN neurons required for egg laying; egl-1 message is detected at low abundance in embryonic and L1 larval mRNA preparations, but not in mRNA preparations from later larval stages or young adults.

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 egl-1;isp-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of egl-1 in SynergyAge

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Species	Gene

Orthologs of isp-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Uqcrfs1