{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T07:57:12Z","timestamp":1772611032303,"version":"3.50.1"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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.<\/jats:p>","DOI":"10.1534\/genetics.119.302326","type":"journal-article","created":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T22:25:12Z","timestamp":1564698312000},"page":"481-490","source":"Crossref","is-referenced-by-count":31,"title":["A Novel Mechanism To Prevent H2S Toxicity in\n                    <i>Caenorhabditis elegans<\/i>"],"prefix":"10.1093","volume":"213","author":[{"given":"Joseph W","family":"Horsman","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frazer I","family":"Heinis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dana L","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Washington School of Medicine, Seattle, Washington 98195"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,10,1]]},"reference":[{"key":"2022011123510281600_bib1","doi-asserted-by":"publisher","first-page":"1882","DOI":"10.1101\/gad.1107803","article-title":"SKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response.","volume":"17","author":"An","year":"2003","journal-title":"Genes Dev."},{"key":"2022011123510281600_bib2","doi-asserted-by":"publisher","first-page":"16275","DOI":"10.1073\/pnas.0508105102","article-title":"Regulation of the Caenorhabditis elegans oxidative stress defense protein SKN-1 by glycogen synthase kinase-3.","volume":"102","author":"An","year":"2005","journal-title":"Proc. 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