ced-13;ced-4;isp-1

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Genetic mutants with ced-13, ced-4, isp-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)
26.32
Lifespan change (compared to wild type)
30.36%
Lifespan comparisons
Triple mutant ced-13(sv32);ced-4(n1162);isp-1(qm150) has a lifespan of 26.32 days, while single mutant ced-13(sv32) has a lifespan of 19.44 days, double mutant ced-4(n1162);isp-1(qm150) has a lifespan of 25.97 days and wild type has a lifespan of 20.19 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)
26.16
Lifespan change (compared to wild type)
27.73%
Lifespan comparisons
Triple mutant ced-13(sv32);ced-4(n1162);isp-1(qm150) has a lifespan of 26.16 days, while single mutant ced-13(sv32) has a lifespan of 19.92 days, double mutant ced-4(n1162);isp-1(qm150) has a lifespan of 27.02 days and wild type has a lifespan of 20.48 days.
Type of interaction
See methods
Contains dependence
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)
25.98
Lifespan change (compared to wild type)
25.27%
Lifespan comparisons
Triple mutant ced-13(sv32);ced-4(n1162);isp-1(qm150) has a lifespan of 25.98 days, while single mutant ced-13(sv32) has a lifespan of 19.37 days, double mutant ced-4(n1162);isp-1(qm150) has a lifespan of 26.02 days and wild type has a lifespan of 20.74 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-13 ced-4 isp-1 ced-13;ced-4;isp-1

Entrez ID
Symbol
GenAge
Wormbase ID

191625
ced-13
View on GenAge (ced-13)
WBGene00000427

hypothetical protein

Locus: CELE_R09F10.9

Wormbase description: ced-13 encodes a 98-residue protein with a single BH3 domain, whose overexpression promotes CED-3/4-dependent apoptosis; CED-13 binds the Bcl-2 ortholog CED-9, and ced-13 is transcriptionally activated by the p53 ortholog CEP-1, and the ced-13 promoter contains several potential p53-binding sites; ced-13 mutations are mostly indistinguishable from wild-type, but may enhance the abnormal response to germline irradiation seen for egl-1 mutations; peptides containing the BH3 domains of either CED-13 or EGL-1 can dissociate stable CED-4/CED-9 heterotetramers in vitro if CED-9 is wild-type, but not if CED-9 has a gain-of-function G169E mutation.

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

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 ced-13;ced-4;isp-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of ced-13 in SynergyAge

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Species	Gene

Orthologs of ced-4 in SynergyAge

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Species	Gene

Orthologs of isp-1 in SynergyAge

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Species	Gene

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Species	Gene
Mus musculus	Uqcrfs1