frh-1;kin-29

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Genetic mutants with frh-1, kin-29 alterations

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

Temperature °C
20
Diet
NGM
Lifespan (days)
16.1
Lifespan change (compared to wild type)
-1.83%
Phenotype
The kinase involved in energy metabolism that we tested (kin-29) affected longevity induced by RNAi-mediated Mit mutants analyzed other than frh-1 RNAi.
Lifespan comparisons
Double mutant frh-1(RNAi);kin-29(gk270) has a lifespan of 16.1 days, while single mutant frh-1(RNAi) has a lifespan of 19.8 days, single mutant kin-29(gk270) has a lifespan of 12.1 days and wild type has a lifespan of 16.4 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: frh-1 kin-29

Entrez ID
Symbol
GenAge
Wormbase ID

174002
frh-1
View on GenAge (frh-1)
WBGene00001486

Frataxin, mitochondrial

Locus: CELE_F59G1.7

Wormbase description: frh-1 encodes the C. elegans frataxin ortholog; by homology, FRH-1 is predicted to be a mitochondrial protein required for biogenesis of iron-sulfur clusters, co-factors necessary for proper function of electron transport chain proteins; in C. elegans, loss of frh-1 activity via RNAi results in small body size, pale coloration, reduced motility, decreased pharyngeal pumping and defecation, reduced egg-laying and fertility, hypersensitivity to oxidative stress, and altered adult lifespan; an frh-1::gfp promoter fusion is expressed in neurons, the pharynx, gut, spermatheca and body wall muscle; in the pharynx, FRH-1 localizes to the mitochondria.

Entrez ID
Symbol
GenAge
Wormbase ID

180574
kin-29
View on GenAge (kin-29)
WBGene00002210

Serine/threonine-protein kinase kin-29

Locus: CELE_F58H12.1

Wormbase description: kin-29 encodes a serine/threonine kinase with significant homology in the kinase domain to the AMP-activated protein kinase (AMPK) and SNF1 kinases; the AMP-kinase cascade is activated by cellular stresses that deplete ATP; AMP-kinase is believed to protect the mammalian cell by 'switching off' ATP-consuming pathways like fatty acid synthesis, by phosphorylating key regulatory enzymes, and switching on alternative pathways for ATP generation; kin-29 is involved in regulating the expression of chemosensory receptors and entry into the dauer pathway; kin-29 also affects body size via interaction with the Sma/Mab pathway and lifespan, with mutants exhibiting a smaller body size and increased life span; a functional KIN-29-GFP fusion protein is expressed in sensory neurons and many other cell types, and localizes to the cytoplasm; under conditions of cellular stress like heat shock, KIN-29-GFP translocates to the nucleus.

Orthologs of frh-1;kin-29 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of frh-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	fh
Mus musculus	Fxn

Orthologs of kin-29 in SynergyAge

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Species	Gene