PXD049417

PXD049417 is an original dataset announced via ProteomeXchange.

Title	Multiomics approach to decipher pathophysiological mechanisms and therapeutic impact of methionine restriction in cystathionine β-synthase deficient homocystinuria
Description	Background. Cystathionine β-synthase (CBS)-deficient homocystinuria (HCU) is an inherited disorder of sulfur amino acid metabolism with varying severity and organ complications, and a limited knowledge about underlying pathophysiological processes. Here we aimed at getting an in-depth insight into disease mechanisms using a transgenic mouse model of HCU (I278T). Methods. We assessed metabolic, proteomic and sphingolipidomic changes, and mitochondrial function in tissues and body fluids of I278T mice and WT controls. Furthermore, we evaluated the efficacy of methionine-restricted diet (MRD) in I278T mice. Results. In WT mice, we observed a distinct tissue/body fluid compartmentalization of metabolites with up to six-orders of magnitude differences in concentrations among various organs. The I278T mice exhibited the anticipated metabolic disbalance with signs of an increased production of hydrogen sulfide and disturbed persulfidation of free aminothiols. HCU resulted in a significant dysregulation of liver proteome affecting biological oxidations, conjugation of compounds, and metabolism of amino acids, vitamins, cofactors and lipids. Liver phospholipidomics indicated upregulation of the pro-proliferative sphingomyelin-ceramide-sphingosine-1-phosphate signaling pathway. Liver mitochondrial function of HCU mice did not seem to be impaired compared to controls. MRD in I278T mice improved metabolic balance in all tissues and substantially reduced dysregulation of liver proteome. Conclusion. The study highlights distinct tissue compartmentalization of sulfur-related metabolites in normal mice, extensive metabolic, proteomic and sphingolipidomic disruptions in I278T mice, and the efficacy of MRD to alleviate some of the HCU-related biochemical abnormalities.
HostingRepository	PRIDE
AnnounceDate	2024-07-03
AnnouncementXML	Submission_2024-07-03_02:18:36.544.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD049417
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Ondrej Vit
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-16 00:27:37	ID requested
⏵ 1	2024-07-03 02:18:37	announced

10.1016/j.redox.2024.103222;

10.6019/PXD049417;

Majtan T, Olsen T, Sokolova J, Krijt J, K, ř, í, ž, kov, á M, Ida T, Ditr, ó, i T, Hansikova H, Vit O, Petrak J, Kucha, ř L, Kruger WD, Nagy P, Akaike T, Ko, ž, ich V, Deciphering pathophysiological mechanisms underlying cystathionine beta-synthase-deficient homocystinuria using targeted metabolomics, liver proteomics, sphingolipidomics and analysis of mitochondrial function. Redox Biol, 73():103222(2024) [pubmed]

submitter keyword: Cystathionine beta-synthase

homocystinuria

methionine restriction

metabolomics

proteomics

Jiri Petrak
contact affiliation	BIOCEV, First Faculty of Medicine, Charles University, 252 50 Vestec, Czech Republic
contact email	jpetr@lf1.cuni.cz
lab head
Ondrej Vit
contact affiliation	Charles University, First Faculty of Medicine, BIOCEV
contact email	ondrvit@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD049417
     1. Label: PRIDE project
     2. Name: Multiomics approach to decipher pathophysiological mechanisms and therapeutic impact of methionine restriction in cystathionine β-synthase deficient homocystinuria