ced-4;egl-1;nuo-6

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Genetic mutants with ced-4, egl-1, nuo-6 alterations

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

Temperature °C
20
Diet
OP50
Lifespan (days)
27.28
Lifespan change (compared to wild type)
40.04%
Lifespan comparisons
Triple mutant ced-4(n1162);egl-1(n1084n3082);nuo-6(qm200) has a lifespan of 27.28 days, while single mutant egl-1(n1084n3082) has a lifespan of 19.16 days, double mutant ced-4(n1162);nuo-6(qm200) has a lifespan of 31.34 days and wild type has a lifespan of 19.48 days.
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)
26.38
Lifespan change (compared to wild type)
31.90%
Lifespan comparisons
Triple mutant ced-4(n1162);egl-1(n1084n3082);nuo-6(qm200) has a lifespan of 26.38 days, while single mutant egl-1(n1084n3082) has a lifespan of 19.1 days, double mutant ced-4(n1162);nuo-6(qm200) has a lifespan of 31.9 days and wild type has a lifespan of 20.0 days.
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)
26.2
Lifespan change (compared to wild type)
34.77%
Lifespan comparisons
Triple mutant ced-4(n1162);egl-1(n1084n3082);nuo-6(qm200) has a lifespan of 26.2 days, while single mutant egl-1(n1084n3082) has a lifespan of 18.96 days, double mutant ced-4(n1162);nuo-6(qm200) has a lifespan of 31.18 days and wild type has a lifespan of 19.44 days.
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: ced-4 egl-1 nuo-6 ced-4;egl-1;nuo-6

Entrez ID
Symbol
GenAge
Wormbase ID

175643
ced-4
View on GenAge (ced-4)
WBGene00000418

Cell death protein 4

Locus: CELE_C35D10.9

Wormbase description: ced-4 encodes a novel protein; along with CED-3, CED-4 is required for the initiation of programmed cell death; accordingly, genetic analyses indicate that ced-3 and ced-4 function upstream of ced-1, ced-2, and nuc-1 in the programmed cell death pathway; in yeast two-hybrid experiments, and upon coexpression in mammalian cells, CED-4 interacts with CED-9, an anti-apoptotic BCL-2 homolog; coexpression of CED-4 and CED-9 results in redistribution of CED-4 from the cytosol to organellar membranes, suggesting that CED-9 may negatively regulate CED-4 activity by sequestering CED-4 to intracellular membranes.

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

172438
nuo-6
View on GenAge (nuo-6)
WBGene00012166

NADH Ubiquinone Oxidoreductase

Locus: CELE_W01A8.4

Wormbase description: nuo-6 encodes the C. elegans ortholog of the NDUFB4/B15 subunit of the mitochondrial NADH dehydrogenase (ubiquinone) complex (complex I).

Orthologs of ced-4;egl-1;nuo-6 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of ced-4 in SynergyAge

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Species	Gene

Orthologs of egl-1 in SynergyAge

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Species	Gene

Orthologs of nuo-6 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Ndufb4
Mus musculus	Ndufb4c
Mus musculus	Ndufb4b