Universität zu Köln

Fu, Chun-Yu ORCID: 0000-0002-5382-528X, Kohl, Joshua B., Liebsch, Filip ORCID: 0000-0002-0955-8065, D’Andrea, Davide, Ditrói, Tamás, Ogata, Seiryo, Neuser, Franziska, Mai, Max, Mellis, Anna T. ORCID: 0000-0002-2027-8750, Kouroussis, Emilia, Morita, Masanobu, Gehling, Titus, Santamaria-Araujo, José Angel, Yeo, Sin Yuin ORCID: 0000-0002-7602-0695, Endepols, Heike ORCID: 0000-0002-6166-4818, Křížková, Michaela, Kozich, Viktor, Krueger, Marcus, Hennermann, Julia B., Barayeu, Uladzimir, Akaike, Takaaki ORCID: 0000-0002-0623-1710, Nagy, Peter, Filipovic, Milos and Schwarz, Guenter ORCID: 0000-0002-2118-9338 (2025). Sulfite oxidase deficiency causes persulfidation loss and hydrogen sulfide release. Journal of Clinical Investigation, 135 (21). pp. 1-17. American Society for Clinical Investigation (ASCI). ISSN 1558-8238

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Abstract

[Artikel-Nr. e181299] 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 S-sulfocysteine, which mediates excitotoxicity, and thiosulfate, a catabolic intermediate/product of hydrogen sulfide (H2S) 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 H2S, 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 H2S 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

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Fu, Chun-Yu UNSPECIFIED https://orcid.org/0000-0002-5382-528X UNSPECIFIED Kohl, Joshua B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Liebsch, Filip UNSPECIFIED https://orcid.org/0000-0002-0955-8065 UNSPECIFIED D’Andrea, Davide UNSPECIFIED UNSPECIFIED UNSPECIFIED Ditrói, Tamás UNSPECIFIED UNSPECIFIED UNSPECIFIED Ogata, Seiryo UNSPECIFIED UNSPECIFIED UNSPECIFIED Neuser, Franziska UNSPECIFIED UNSPECIFIED UNSPECIFIED Mai, Max UNSPECIFIED UNSPECIFIED UNSPECIFIED Mellis, Anna T. UNSPECIFIED https://orcid.org/0000-0002-2027-8750 UNSPECIFIED Kouroussis, Emilia UNSPECIFIED UNSPECIFIED UNSPECIFIED Morita, Masanobu UNSPECIFIED UNSPECIFIED UNSPECIFIED Gehling, Titus UNSPECIFIED UNSPECIFIED UNSPECIFIED Santamaria-Araujo, José Angel UNSPECIFIED UNSPECIFIED UNSPECIFIED Yeo, Sin Yuin UNSPECIFIED https://orcid.org/0000-0002-7602-0695 UNSPECIFIED Endepols, Heike UNSPECIFIED https://orcid.org/0000-0002-6166-4818 UNSPECIFIED Křížková, Michaela UNSPECIFIED UNSPECIFIED UNSPECIFIED Kozich, Viktor UNSPECIFIED UNSPECIFIED UNSPECIFIED Krueger, Marcus UNSPECIFIED UNSPECIFIED UNSPECIFIED Hennermann, Julia B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Barayeu, Uladzimir UNSPECIFIED UNSPECIFIED UNSPECIFIED Akaike, Takaaki UNSPECIFIED https://orcid.org/0000-0002-0623-1710 UNSPECIFIED Nagy, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Filipovic, Milos UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwarz, Guenter UNSPECIFIED https://orcid.org/0000-0002-2118-9338 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-798232
Identification Number:	10.1172/JCI181299
Journal or Publication Title:	Journal of Clinical Investigation
Volume:	135
Number:	21
Page Range:	pp. 1-17
Date:	3 November 2025
Publisher:	American Society for Clinical Investigation (ASCI)
ISSN:	1558-8238
Language:	English
Faculty:	Central Institutions / Interdisciplinary Research Centers Faculty of Mathematics and Natural Sciences Faculty of Medicine
Divisions:	Außeruniversitäre Forschungseinrichtungen > Forschungszentrum Jülich CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry Faculty of Medicine > Radiologische Diagnostik > Institut und Poliklinik für Radiologische Diagnostik Zentrum für Molekulare Medizin
Subjects:	Chemistry and allied sciences Life sciences Medical sciences Medicine
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/79823