RRC ID 58147
Author Horsman JW, Heinis FI, Miller DL.
Title A Novel Mechanism To Prevent H2S Toxicity in Caenorhabditis elegans.
Journal Genetics
Abstract Hydrogen sulfide (H2S) is an endogenously produced signaling molecule that can be cytoprotective, especially in conditions of ischemia/reperfusion injury. However, H2S is also toxic, and unregulated accumulation or exposure to environmental H2S can be lethal. In Caenorhabditis elegans, the hypoxia inducible factor (hif-1) coordinates the initial transcriptional response to H2S, and is essential to survive exposure to low concentrations of H2S. We performed a forward genetic screen to identify mutations that suppress the lethality of hif-1 mutant animals in H2S. The mutations we recovered are specific for H2S, as they do not suppress embryonic lethality or reproductive arrest of hif-1 mutant animals in hypoxia, nor can they prevent the death of hif-1 mutant animals exposed to hydrogen cyanide. The majority of hif-1 suppressor mutations we recovered activate the skn-1/Nrf2 transcription factor. Activation of SKN-1 by hif-1 suppressor mutations increased the expression of a subset of H2S-responsive genes, consistent with previous findings that skn-1 plays a role in the transcriptional response to H2S. Using transgenic rescue, we show that overexpression of a single gene, rhy-1, is sufficient to protect hif-1 mutant animals in H2S. The rhy-1 gene encodes a predicated O-acyltransferase enzyme that has previously been shown to negatively regulate HIF-1 activity. Our data indicate that RHY-1 has novel, hif-1 independent, function that promotes survival in H2S.
Volume 213(2)
Pages 481-490
Published 2019-10-1
DOI 10.1534/genetics.119.302326
PII genetics.119.302326
PMID 31371406
PMC PMC6781907
MeSH Acyltransferases / genetics* Animals Caenorhabditis elegans / drug effects Caenorhabditis elegans / genetics* Caenorhabditis elegans Proteins / genetics* DNA-Binding Proteins / genetics Gene Expression Regulation / drug effects Green Fluorescent Proteins / genetics Hydrogen Cyanide / toxicity Hydrogen Sulfide / metabolism Hydrogen Sulfide / toxicity* Hypoxia / genetics Hypoxia / metabolism Mutation Synthetic Lethal Mutations / drug effects Transcription Factors / genetics*
IF 3.564
Times Cited 2
C.elegans tm3378