PXD067204

PXD067204 is an original dataset announced via ProteomeXchange.

Title	Integrated Multi-Omics Mapping of Mitochondrial Dysfunction and Substrate Preference in Barth Syndrome Cardiac Tissue
Description	Barth syndrome (BTHS) is a rare X-linked recessively inherited disorder caused by variants in the TAFAZZIN gene. The pathogenic variants lead to impaired conversion of monolysocardiolipin (MLCL) into mature phospholipid cardiolipin (CL). The accumulation of MLCL and mature CL deficiency is a diagnostic marker for BTHS. The clinical spectrum includes cardiomyopathy, skeletal myopathy, neutropenia, and delays in growth. In severely affected BTHS patients, the cardiac phenotype is early onset, heterogeneous and unpredictable. Ultimately, these patients may require a cardiac transplant early in their life. Unfortunately, the pathophysiological mechanisms of BTHS are poorly understood, and treatment options for BTHS remain symptomatic. In this study, we analysed heart samples from five paediatric male BTHS individuals (5 month-15 years old) and compared them to tissues from 24 non-failing donors (19-71 years old) using a newly developed integrated omics method that combines metabolomics, lipidomics and proteomics using a single sample. This comprehensive analysis confirms expected changes in established diagnostic markers such as CL and MLCL, as well as severe and pleiotropic alterations in mitochondrial phenotype and metabolic output, a substrate shift in energy metabolism, and an elevation of heart-failure markers. It also reveals striking interindividual differences between BTHS individuals. Combined, we describe a powerful analytical tool for the in-depth analysis of metabolic disorders and a solid foundation for the understanding of BTHS disease phenotypes in cardiac tissues.
HostingRepository	PRIDE
AnnounceDate	2025-09-08
AnnouncementXML	Submission_2025-09-08_01:12:38.878.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bauke Schomakers
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-11 10:14:24	ID requested
⏵ 1	2025-09-08 01:12:39	announced

10.15252/EMMM.202521835;

ProteomeXchange project tag: Cardiovascular (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project, Mitochondria (HPP)

submitter keyword: Heart Barth multi-omics

Riekelt H. Houtkooper
contact affiliation	Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
contact email	r.h.houtkooper@amsterdamumc.nl
lab head
Bauke Schomakers
contact affiliation	Laboratory Genetic Metabolic Diseases, Amsterdam University Medical Centers, University of Amsterdam, The Netherlands.
contact email	b.schomakers@amsterdamumc.nl
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/09/PXD067204

PRIDE project URI

• PRIDE
  1. PXD067204
     1. Label: PRIDE project
     2. Name: Integrated Multi-Omics Mapping of Mitochondrial Dysfunction and Substrate Preference in Barth Syndrome Cardiac Tissue