isp-1;par-4

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Genetic mutants with isp-1, par-4 alterations

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

Temperature °C
20
Diet
NGM
Lifespan (days)
29.9
Lifespan change (compared to wild type)
73.84%
Phenotype
The kinase involved in energy metabolism that we tested (par-4) affected longevity induced by RNAi-mediated Mit mutants analyzed other than isp-1 RNAi.
Lifespan comparisons
Double mutant isp-1(RNAi);par-4(it57) has a lifespan of 29.9 days, while single mutant isp-1(RNAi) has a lifespan of 30.3 days, single mutant par-4(it57) has a lifespan of 16.8 days and wild type has a lifespan of 17.2 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Schiavi A et al., 2013, Autophagy induction extends lifespan and reduces lipid content in response to frataxin silencing in C. elegans. Exp Gerontol. 48(2):191-201 23247094 Click here to select all mutants from this PubMed ID in the graph
Abstract
Severe mitochondria deficiency leads to a number of devastating degenerative disorders, yet, mild mitochondrial dysfunction in different species, including the nematode Caenorhabditis elegans, can have pro-longevity effects. This apparent paradox indicates that cellular adaptation to partial mitochondrial stress can induce beneficial responses, but how this is achieved is largely unknown. Complete absence of frataxin, the mitochondrial protein defective in patients with Friedreich's ataxia, is lethal in C. elegans, while its partial deficiency extends animal lifespan in a p53 dependent manner. In this paper we provide further insight into frataxin control of C. elegans longevity by showing that a substantial reduction of frataxin protein expression is required to extend lifespan, affect sensory neurons functionality, remodel lipid metabolism and trigger autophagy. We find that Beclin and p53 genes are required to induce autophagy and concurrently reduce lipid storages and extend animal lifespan in response to frataxin suppression. Reciprocally, frataxin expression modulates autophagy in the absence of p53. Human Friedreich ataxia-derived lymphoblasts also display increased autophagy, indicating an evolutionarily conserved response to reduced frataxin expression. In sum, we demonstrate a causal connection between induction of autophagy and lifespan extension following reduced frataxin expression, thus providing the rationale for investigating autophagy in the pathogenesis and treatment of Friedreich's ataxia and possibly other human mitochondria-associated disorders.

Search genes: isp-1 par-4

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.

Entrez ID
Symbol
GenAge
Wormbase ID

180185
par-4
View on GenAge (par-4)
WBGene00003919

Serine/threonine-protein kinase par-4

Locus: CELE_Y59A8B.14

Wormbase description: par-4 encodes a serine-threonine kinase that is homologous to the human LKB1 kinase, mutations in which are associated with the cancer predisposition Peutz-Jeghers syndrome; par-4 activity is required for several development processes, including establishment of embryonic asymmetry, lifespan extension, response to oxidative stress and inhibition of germline proliferation during dauer larvae formation; genetic analyses suggest that in regulating the response to oxidative stress, par-4 acts upstream of aak-2 and that in regulating germ cell proliferation in dauers, par-4 acts upstream of aak-1 and in parallel to aak-2; PAR-4 is present in embryos, L4 larvae, males, and adult hermaphrodites; in the hermaphrodite gonad, PAR-4 is present at the actin-rich boundaries between syncytial nuclei, while in early embryos PAR-4 is present in the cytoplasm and at the cellular cortex; PAR-4 binds bovine calmodulin in vitro in a calcium-dependent manner.

Orthologs of isp-1;par-4 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Stk11;Uqcrfs1
Mus musculus	Uqcrfs1;Stk11

Orthologs of isp-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Uqcrfs1

Orthologs of par-4 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Lkb1
Mus musculus	Stk11