PXD045896

PXD045896 is an original dataset announced via ProteomeXchange.

Title	Sulfite oxidase-deficient mice disclose a novel contribution of hydrogen sulfide to the pathomechanism of sulfite toxicity
Description	Sulfite oxidase (SOX) deficiency is a rare inborn error in metabolism resulting in severe neurological damage. As terminal intermediate of cysteine cataboilism, sulfite accumulats to toxic levels causing a raise in downstream products such as S-sulfocysteine (SSC), mediating excitotoxic action, and thiosulfate, a catabolic end product of H2S metabolism. SOX is a molybdenum cofactor dependent enzyme and patients with defects in the biogenesis of Moco exhibit similar symptoms as patients with SOX deficiency. Here, we generated a first full-body knock-out mouse model for isolated SOX deficiency (iSOD). Homozygous SuoxKO/KO mice were severely impaired with an average lifespan of 9.6 days. Surprisingly, they show no neuropathological phenotype as observed in human patients. Biomarkers such as sulfite and SSC were only moderately increased in urine, while thiosulfate showed strongest, 45-fold accumulation in urine of SuoxKO/KO mice. To our surprise, the metabolic precursor of thiosulfate, H2S was only two-fold increae in plasma being consistent with no major change in H2S metabolism. As primary source of the massive thiosulfate excretion we identified a loss in a global protein persulfidation due to sulfite accumulation in SuoxKO/KO mice liver extracts resulting in the liberation of H2S. Mass spectrometric analysis of the global protein persulfidome identified a major loss of S-persulfidation in enzymes involved in amino acids and fatty acid metabolism. In aggregate our study identified a noivel contribution of H2S metabolism and persulfidation in the pathomechanism of iSOD, which also applies to patients suffering from molybdenum cofactor deficiency. Using chemoproteomic approaches, we assessed persulfidation levels in WT and SUOX-/- mice liver. To ensure that persulfidation changes were not due to the protein expression changes, we also measured the total proteome in the same samples.
HostingRepository	PRIDE
AnnounceDate	2025-10-13
AnnouncementXML	Submission_2025-10-13_13:40:04.970.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD045896
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Davide D´Andrea
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-04 04:46:55	ID requested
⏵ 1	2025-10-13 13:40:05	announced

10.6019/PXD045896;

10.1172/JCI181299;

submitter keyword: Persulfidation, SUOX, Sulfite oxidase

Milos Filipovic
contact affiliation	SULFAGING group, Leibniz-Institut für Analytische Wissenschaften – ISAS – e.V. DORTMUND Germany
contact email	milos.filipovic@isas.de
lab head
Davide D´Andrea
contact affiliation	Leibniz-Institut für Analytische Wissenschaften - ISAS
contact email	davide.dandrea@isas.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045896
     1. Label: PRIDE project
     2. Name: Sulfite oxidase-deficient mice disclose a novel contribution of hydrogen sulfide to the pathomechanism of sulfite toxicity