bec-1;frh-1

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Genetic mutants with bec-1, frh-1 alterations

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

Temperature °C
20
Diet
NGM
Lifespan (days)
16.7
Lifespan change (compared to wild type)
-9.24%
Phenotype
RNAi of bec-1 shortened animal lifespan, and completely abolished the lifespan extension induced by frh-1 RNAi.
Lifespan comparisons
Double mutant bec-1(RNAi);frh-1(RNAi) has a lifespan of 16.7 days, while single mutant bec-1(RNAi) has a lifespan of 16.8 days, single mutant frh-1(RNAi) has a lifespan of 23.1 days and wild type has a lifespan of 18.4 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.

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

Temperature °C
20
Diet
NGM
Lifespan (days)
8.4
Lifespan change (compared to wild type)
-54.35%
Phenotype
Genetic suppression of bec-1 shortened animal lifespan, and completely abolished the lifespan extension induced by frh-1 RNAi.
Lifespan comparisons
Double mutant bec-1(ok691);frh-1(RNAi) has a lifespan of 8.4 days, while single mutant frh-1(RNAi) has a lifespan of 23.1 days, single mutant bec-1(ok691) has a lifespan of 9.9 days and wild type has a lifespan of 18.4 days.
Type of interaction
See methods
Enhancer, opposite lifespan effects
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: bec-1 frh-1

Entrez ID
Symbol
GenAge
Wormbase ID

177345
bec-1
View on GenAge (bec-1)
WBGene00000247

Beclin homolog

Locus: CELE_T19E7.3

Wormbase description: bec-1 encodes a coiled-coil protein orthologous to the yeast and mammalian autophagy proteins Atg6/Vps30/Beclin1; by homology, BEC-1 may be part of a Class III phosphatidylinositol 3-kinase complex that plays a role in localizing autophagy proteins to preautophagosomal structures and overexpression of C. elegans bec-1 in S. cerevisiae APG6/VPS30 mutants can rescue associated autophagy defects; bec-1 is also required for regulation of endocytic retrograde transport; in C. elegans, bec-1 activity is required for normal dauer morphogenesis and survival of dauer larvae, as well as for adult life span extension of daf-2(e1370) mutants at 15 degrees; in addition, bec-1(RNAi) indicates a role for bec-1 in normal growth rates, movement, and vulval morphogenesis; a bec-1::GFP reporter fusion is expressed in the hypodermis, intestine, nervous system, pharynx, and reproductive organs, all tissues that are remodeled during dauer larval development.

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.

Orthologs of bec-1;frh-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Atg6;fh
Mus musculus	Becn1;Fxn

Orthologs of bec-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Atg6
Mus musculus	Becn1

Orthologs of frh-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	fh
Mus musculus	Fxn