{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:47:30Z","timestamp":1787312850214,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T00:00:00Z","timestamp":1677456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Mandema stipend from the UMCG and a Kolff grant","award":["16OKG06"],"award-info":[{"award-number":["16OKG06"]}]},{"name":"Dutch Kidney Foundation","award":["16OKG06"],"award-info":[{"award-number":["16OKG06"]}]},{"name":"UMCG awarde","award":["16OKG06"],"award-info":[{"award-number":["16OKG06"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>The protective effects of hydrogen sulphide (H2S) to limit oxidative injury and preserve mitochondrial function during sepsis, ischemia\/reperfusion, and neurodegenerative diseases have prompted the development of soluble H2S-releasing compounds such as GYY4137. Yet, the effects of GYY4137 on the mitochondrial function of endothelial cells remain unclear, while this cell type comprises the first target cell after parenteral administration. Here, we specifically assessed whether human endothelial cells possess a functional sulfide:quinone oxidoreductase (SQOR), to oxidise GYY4137-released H2S within the mitochondria for electron donation to the electron transport chain. We demonstrate that H2S administration increases oxygen consumption by human umbilical vein endothelial cells (HUVECs), which does not occur in the SQOR-deficient cell line SH-SY5Y. GYY4137 releases H2S in HUVECs in a dose- and time-dependent fashion as quantified by oxygen consumption and confirmed by lead acetate assay, as well as AzMC fluorescence. Scavenging of intracellular H2S using zinc confirmed intracellular and intramitochondrial sulfur, which resulted in mitotoxic zinc sulfide (ZnS) precipitates. Together, GYY4137 increases intramitochondrial H2S and boosts oxygen consumption of endothelial cells, which is likely governed via the oxidation of H2S by SQOR. This mechanism in endothelial cells may be instrumental in regulating H2S levels in blood and organs but can also be exploited to quantify H2S release by soluble donors such as GYY4137 in living systems.<\/jats:p>","DOI":"10.3390\/antiox12030587","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T03:52:21Z","timestamp":1677469941000},"page":"587","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["GYY4137-Derived Hydrogen Sulfide Donates Electrons to the Mitochondrial Electron Transport Chain via Sulfide: Quinone Oxidoreductase in Endothelial Cells"],"prefix":"10.3390","volume":"12","author":[{"given":"Bastiaan S.","family":"Star","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth C.","family":"van der Slikke","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Ransy","sequence":"additional","affiliation":[{"name":"The National Center for Scientific Research (CNRS), The National Institute of Health and Medical Research (Inserm), Universit\u00e9 de Paris, F-75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Schmitt","sequence":"additional","affiliation":[{"name":"The National Center for Scientific Research (CNRS), The National Institute of Health and Medical Research (Inserm), Universit\u00e9 de Paris, F-75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5135-4621","authenticated-orcid":false,"given":"Robert H.","family":"Henning","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7518-9237","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric","family":"Bouillaud","sequence":"additional","affiliation":[{"name":"The National Center for Scientific Research (CNRS), The National Institute of Health and Medical Research (Inserm), Universit\u00e9 de Paris, F-75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1032-321X","authenticated-orcid":false,"given":"Hjalmar R.","family":"Bouma","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands"},{"name":"Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s00395-005-0569-9","article-title":"Exogenous hydrogen sulfide (H2S) protects against regional myocardial ischemia-reperfusion injury\u2014Evidence for a role of K ATP channels","volume":"101","author":"Johansen","year":"2006","journal-title":"Basic Res. 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