Sulfite oxidase deficiency causes persulfidation loss and hydrogen sulfide release
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F25%3A10506531" target="_blank" >RIV/00216208:11110/25:10506531 - isvavai.cz</a>
Alternative codes found
RIV/00064165:_____/25:10506531
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=D8l3lFTX_k" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=D8l3lFTX_k</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1172/JCI181299" target="_blank" >10.1172/JCI181299</a>
Alternative languages
Result language
angličtina
Original language name
Sulfite oxidase deficiency causes persulfidation loss and hydrogen sulfide release
Original language description
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.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30101 - Human genetics
Result continuities
Project
<a href="/en/project/NU23-07-00383" target="_blank" >NU23-07-00383: RAre DIsorders of SUlfur amino acid Metabolism: deep phenotyping and development of novel diagnostic approaches (RADISUM)</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Clinical Investigation
ISSN
0021-9738
e-ISSN
1558-8238
Volume of the periodical
135
Issue of the periodical within the volume
21
Country of publishing house
US - UNITED STATES
Number of pages
16
Pages from-to
e181299
UT code for WoS article
001650704800008
EID of the result in the Scopus database
2-s2.0-105020770901