hlh-30;mxl-3

There is no network for this step.

Fullscreen mode

Hide graph

Legend

Genetic mutants with hlh-30, mxl-3 alterations

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

Temperature °C
20
Diet
NGM; OP50
Lifespan (days)
21.0
Lifespan change (compared to wild type)
5.00%
Phenotype
The hlh-30 mutants were modestly short lived and loss of hlh-30 function suppressed the longevity phenotype of mxl-3 mutants .
Lifespan comparisons
Double mutant hlh-30(tm1978);mxl-3(ok1947) has a lifespan of 21.0 days, while single mutant hlh-30(tm1978) has a lifespan of 18.0 days, single mutant mxl-3(ok1947) has a lifespan of 28.0 days and wild type has a lifespan of 20.0 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
O'Rourke EJ, Ruvkun G, 2013, MXL-3 and HLH-30 transcriptionally link lipolysis and autophagy to nutrient availability. Nat Cell Biol. 15(6):668-76 23604316 Click here to select all mutants from this PubMed ID in the graph
Abstract
Fat is stored or mobilized according to food availability. Malfunction of the mechanisms that ensure this coordination underlie metabolic diseases in humans. In mammals, lysosomal and autophagic function is required for normal fat storage and mobilization in the presence or absence of food. Autophagy is tightly linked to nutrients. However, if and how lysosomal lipolysis is coupled to nutritional status remains to be determined. Here we identify MXL-3 and HLH-30 (TFEB orthologue) [corrected] as transcriptional switches coupling lysosomal lipolysis and autophagy to nutrient availability and controlling fat storage and ageing in Caenorhabditis elegans. Transcriptional coupling of lysosomal lipolysis and autophagy to nutrients is also observed in mammals. Thus, MXL-3 and HLH-30 orchestrate an adaptive and conserved cellular response to nutritional status and regulate lifespan.

Search genes: hlh-30 mxl-3

Entrez ID
Symbol
GenAge
Wormbase ID

177157
hlh-30
View on GenAge (hlh-30)
WBGene00020930

Helix Loop Helix

Locus: CELE_W02C12.3

Wormbase description: hlh-30 encodes a predicted basic helix-loop-helix (bHLH) transcription factor, one of 42 such genes in the C. elegans genome, it is spliced to give 18 different transcripts; it is orthologous to human microphthalmia-associated transcription factor (HGNC:MITF); loss of hlh-30 activity via RNAi results in reduced fat storage; HLH-30 demonstrates sequence-specific DNA binding for the E box sequence CACGTG and likely binds DNA as a homodimer; expression profiles of hlh-30 mutants indicate that, like its human ortholog, HLH-30 regulates expression of genes involved in metabolism; at least one of the bHLH protein isoforms appears to be important for an infection-specific immune response to M. nematophilum, though the overall induction of this gene following infection was not appreciable (1.3-fold).

Entrez ID
Symbol
GenAge
Wormbase ID

181457
mxl-3
View on GenAge (mxl-3)
WBGene00003511

MaX-Like

Locus: CELE_F46G10.6

Wormbase description: mxl-3 encodes a basic helix-loop-helix transcription factor; an mxl-3 deletion mutation, tm2580, has been reported to exhibit a slight growth delay; in vitro, MXL-3 binds E-box and/or E-box-like sequences; an mxl-3 reporter fusion is expressed in larvae and adults and seen in head muscles and neurons, part of the intestine, and body hypodermis.

Orthologs of hlh-30;mxl-3 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of hlh-30 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Mitf
Mus musculus	Tfe3
Mus musculus	Tfeb
Mus musculus	Tfec

Orthologs of mxl-3 in SynergyAge

Show in SynergyAge
Species	Gene

About

SynergyAge database hosts high-quality, manually curated information about the synergistic and antagonistic lifespan effects of genetic interventions in model organisms, also allowing users to explore the longevity relationships between genes in a visual way.