RRC ID 53439
著者 Horsman JW, Miller DL.
タイトル Mitochondrial Sulfide Quinone Oxidoreductase Prevents Activation of the Unfolded Protein Response in Hydrogen Sulfide.
ジャーナル J Biol Chem
Abstract Hydrogen sulfide (H2S) is an endogenously produced gaseous molecule with important roles in cellular signaling. In mammals, exogenous H2S improves survival of ischemia/reperfusion. We have previously shown that exposure to H2S increases the lifespan and thermotolerance in Caenorhabditis elegans, and improves protein homeostasis in low oxygen. The mitochondrial SQRD-1 (sulfide quinone oxidoreductase) protein is a highly conserved enzyme involved in H2S metabolism. SQRD-1 is generally considered important to detoxify H2S. Here, we show that SQRD-1 is also required to maintain protein translation in H2S. In sqrd-1 mutant animals, exposure to H2S leads to phosphorylation of eIF2α and inhibition of protein synthesis. In contrast, global protein translation is not altered in wild-type animals exposed to lethally high H2S or in hif-1(ia04) mutants that die when exposed to low H2S. We demonstrate that both gcn-2 and pek-1 kinases are involved in the H2S-induced phosphorylation of eIF2α. Both ER and mitochondrial stress responses are activated in sqrd-1 mutant animals exposed to H2S, but not in wild-type animals. We speculate that SQRD-1 activity in H2S may coordinate proteostasis responses in multiple cellular compartments.
巻・号 291(10)
ページ 5320-5
公開日 2016-3-4
DOI 10.1074/jbc.M115.697102
PII S0021-9258(20)43167-9
PMID 26677221
PMC PMC4777863
MeSH Animals Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Carrier Proteins / genetics Carrier Proteins / metabolism Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism Eukaryotic Initiation Factor-2 / metabolism Hydrogen Sulfide / metabolism* Hydrogen Sulfide / toxicity MAP Kinase Kinase 1 / genetics MAP Kinase Kinase 1 / metabolism Oxidoreductases Acting on Sulfur Group Donors / genetics Oxidoreductases Acting on Sulfur Group Donors / metabolism* Transcription Factors / genetics Transcription Factors / metabolism Unfolded Protein Response*
IF 4.238
引用数 5
リソース情報
線虫 tm3378