{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T06:22:05Z","timestamp":1793773325834,"version":"4.6.1"},"reference-count":64,"publisher":"American Society for Clinical Investigation","issue":"21","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["SFB1218,project number,269925409"],"award-info":[{"award-number":["SFB1218,project number,269925409"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["SFB1403 project number 414786233"],"award-info":[{"award-number":["SFB1403 project number 414786233"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"name":"European Research Council","award":["Grant Agreement No. 864921"],"award-info":[{"award-number":["Grant Agreement No. 864921"]}]},{"name":"National Research, Development and Innovation Office","award":["2022-2.1.1-NL-2022-00010"],"award-info":[{"award-number":["2022-2.1.1-NL-2022-00010"]}]},{"name":"Hungarian Thematic Excellence Program","award":["project TKP2021-EGA-44"],"award-info":[{"award-number":["project TKP2021-EGA-44"]}]},{"DOI":"10.13039\/100020916","name":"Hungarian Research Network","doi-asserted-by":"crossref","award":["HUN-REN\u2013UVMB,grant 15002"],"award-info":[{"award-number":["HUN-REN\u2013UVMB,grant 15002"]}],"id":[{"id":"10.13039\/100020916","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100009553","name":"Czech Health Research Council","doi-asserted-by":"crossref","award":["NU23-07-00383"],"award-info":[{"award-number":["NU23-07-00383"]}],"id":[{"id":"10.13039\/501100009553","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100016366","name":"General University Hospital in Prague","doi-asserted-by":"crossref","award":["RVO-VFN 64165"],"award-info":[{"award-number":["RVO-VFN 64165"]}],"id":[{"id":"10.13039\/501100016366","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,3]]},"abstract":"<jats:p>\n                    Sulfite oxidase (SOX) deficiency is a rare inborn error of cysteine metabolism resulting in severe neurological damage. In patients, sulfite accumulates to toxic levels, causing a rise in the downstream products\n                    <jats:italic>S<\/jats:italic>\n                    -sulfocysteine, which mediates excitotoxicity, and thiosulfate, a catabolic intermediate\/product of hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S) metabolism. Here, we report a full-body knockout mouse model for SOX deficiency (SOXD) with a severely impaired phenotype. Among the urinary biomarkers, thiosulfate showed a 45-fold accumulation in SOXD mice, representing the major excreted S-metabolite. Consistently, we found increased plasma H\n                    <jats:sub>2<\/jats:sub>\n                    S, which was derived from sulfite-induced release from persulfides, as demonstrated in vitro and in vivo. Mass spectrometry analysis of total protein persulfidome identified a major loss of S-persulfidation in 20% of the proteome, affecting enzymes in amino acids, fatty acid metabolism, and cytosolic iron-sulfur cluster biogenesis. Urinary amino acid profiles indicated metabolic rewiring and mitochondrial dysfunction, thus identifying an altered H\n                    <jats:sub>2<\/jats:sub>\n                    S metabolism and persulfidation in SOXD. Finally, oxidized glutathione and glutathione trisulfide were able to scavenge sulfite in vitro and in vivo, extending the lifespan of SOXD mice and providing a mechanistic concept of sulfite scavenging for the treatment of this severe metabolic disorder of cysteine catabolism.\n                  <\/jats:p>","DOI":"10.1172\/jci181299","type":"journal-article","created":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T19:01:03Z","timestamp":1762110063000},"source":"Crossref","is-referenced-by-count":8,"title":["Sulfite oxidase deficiency causes persulfidation loss and hydrogen sulfide release"],"prefix":"10.1172","volume":"135","author":[{"given":"Chun-Yu","family":"Fu","sequence":"first","affiliation":[{"name":"Institute of Biochemistry, Department of Chemistry and Biochemistry, University of Cologne, Cologne, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua B.","family":"Kohl","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Department of Chemistry and Biochemistry, University of Cologne, Cologne, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip","family":"Liebsch","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Department of Chemistry and Biochemistry, University of Cologne, Cologne, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"D\u2019Andrea","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Analytical Sciences, ISAS e.V., Dortmund, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"Ditr\u00f3i","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiryo","family":"Ogata","sequence":"additional","affiliation":[{"name":"Department of 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Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Kouroussis","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Analytical Sciences, ISAS e.V., Dortmund, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanobu","family":"Morita","sequence":"additional","affiliation":[{"name":"Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Titus","family":"Gehling","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Department of Chemistry and Biochemistry, University of Cologne, Cologne, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Angel","family":"Santamaria-Araujo","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Department of Chemistry and Biochemistry, University of Cologne, Cologne, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sin Yuin","family":"Yeo","sequence":"additional","affiliation":[{"name":"Institute of Diagnostic and Interventional Radiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Endepols","sequence":"additional","affiliation":[{"name":"Institute of Radiochemistry and Experimental Molecular Imaging and"},{"name":"Department of Nuclear Medicine, University of Cologne, Faculty of Medicine, and University Hospital Cologne, Cologne, Germany."},{"name":"Forschungszentrum J\u00fclich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), J\u00fclich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"K\u0159\u00ed\u017ekov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Inherited Metabolic Disorders, Charles University, First Faculty of Medicine, and General University Hospital in Prague, 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An almost final solution to the ethylmalonic acid syndrome. Paper presented at: ERDIM Scientific and DPT Meeting; October 22\u201323, 2009; San Diego, California, USA. https:\/\/www.erndim.org\/wp-content\/uploads\/2021\/08\/A-final-solution-to-the-ethylmalonic-acid-syndrome.pdf Accessed September 4, 2025"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1086\/381653"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.202000661"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102517"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5392.1321"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.26.3309"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-016-1676-4"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20140768"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2019.04.006"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.602664"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20130051"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20051510"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2014.09.007"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.201402312"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.672816"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1500968"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1039\/C5SC04818D"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201305876"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2024.12.008"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2020.118863"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32006-8"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20170559"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1907"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.100950"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1142"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.03737.x"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-022-01145-w"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-21677-4"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12730"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1177\/088307380101600406"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2013.04.001"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2010.04.004"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1021\/bi300778t"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-49014-2"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12232"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23363-x"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22126452"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.965965"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2015.10.016"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2022.0064"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2023.0352"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1186\/s12896-016-0234-4"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp030"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq330"},{"key":"B63"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp426"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/181299\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T17:59:21Z","timestamp":1779213561000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/181299"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,3]]},"references-count":64,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,8,28]]},"published-print":{"date-parts":[[2025,11,3]]}},"alternative-id":["10.1172\/JCI181299"],"URL":"https:\/\/doi.org\/10.1172\/jci181299","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,3]]},"article-number":"e181299"}}