dc.contributor.author | Vitvitsky, V | |
dc.contributor.author | Miljkovic, JL | |
dc.contributor.author | Bostelaar, T | |
dc.contributor.author | Adhikari, B | |
dc.contributor.author | Yadav, PK | |
dc.contributor.author | Steiger, AK | |
dc.contributor.author | Torregrossa, R | |
dc.contributor.author | Pluth, MD | |
dc.contributor.author | Whiteman, M | |
dc.contributor.author | Banerjee, R | |
dc.contributor.author | Filipovic, MR | |
dc.date.accessioned | 2018-07-31T11:16:08Z | |
dc.date.issued | 2018-07-18 | |
dc.description.abstract | Hydrogen sulfide (H2S) is an endogenously produced gas that is toxic at high concentrations. It is eliminated by a dedicated mitochondrial sulfide oxidation pathway, which connects to the electron transfer chain at the level of complex III. Direct reduction of cytochrome c (Cyt C) by H2S has been reported previously but not characterized. In this study, we demonstrate that reduction of ferric Cyt C by H2S exhibits hysteretic behavior, which suggests the involvement of reactive sulfur species in the reduction process and is consistent with a reaction stoichiometry of 1.5 mol of Cyt C reduced/mol of H2S oxidized. H2S increases O2 consumption by human cells (HT29 and HepG2) treated with the complex III inhibitor antimycin A, which is consistent with the entry of sulfide-derived electrons at the level of complex IV. Cyt C-dependent H2S oxidation stimulated protein persulfidation in vitro, while silencing of Cyt C expression decreased mitochondrial protein persulfidation in a cell culture. Cyt C released during apoptosis was correlated with persulfidation of procaspase 9 and with loss of its activity. These results reveal a potential role for the electron transfer chain in general, and Cyt C in particular, for potentiating sulfide-based signaling. | en_GB |
dc.description.sponsorship | This work was supported by the French State in the frame of the “Investments for the future” Programme IdEx Bordeaux, reference ANR-10-IDEX-03-02, and by an ATIP-AVENIR grant (to M.R.F.), the National Institutes of Health (GM112455 to R.B. and R01GM113030 to M.D.P.), the Medical Research Council, UK (MR/M022706/1 to M.W.), the National Science Foundation (DGE-1309047 to A.K.S.), and the Brian Ridge Scholarship (R.T.). The authors are grateful to M.-F. Giraud for the help with purification of mitochondria. | en_GB |
dc.identifier.citation | Published online 2 July 2018 | en_GB |
dc.identifier.doi | 10.1021/acschembio.8b00463 | |
dc.identifier.uri | http://hdl.handle.net/10871/33604 | |
dc.language.iso | en | en_GB |
dc.publisher | American Chemical Society | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/29966080 | en_GB |
dc.rights.embargoreason | Under embargo until 2 July 2019 in compliance with publisher policy. | en_GB |
dc.rights | © 2018. American Chemical Society, All rights reserved. | en_GB |
dc.title | Cytochrome c Reduction by H2S Potentiates Sulfide Signaling. | en_GB |
dc.type | Article | en_GB |
exeter.place-of-publication | United States | en_GB |
dc.description | This is the author accepted manuscript. The final version is available from American Chemical Society via the DOI in this record. | en_GB |
dc.identifier.journal | ACS Chemical Biology | en_GB |