PXD072978

PXD072978 is an original dataset announced via ProteomeXchange.

Title	A biallelic MRPL42variant causes a combined oxidative phosphorylation deficiency syndrome revealed by multi-omics
Description	Pathogenic variants affecting components of the mitochondrial translation machinery lead to various impairments of mitochondrial function and thereby cause a spectrum of multisystem diseases. In an infant with a fatal, metabolic multisystem condition we performed a comprehensive multi-omics approach and detected the intronic biallelic variant NM_014050.4:c.219+6 T > A in MRPL42 (mitochondrial ribosomal protein L42) encoding a component of the large mitochondrial ribosomal subunit. RNA-seq revealed a strong reduction and aberrant splicing of the majority of MRPL42 transcripts leading to a frameshift and thereby to a premature termination codon: p.(Asn46Leufs*18). However, additional use of the canonical splice site led to a low residual expression of the wildtype transcript and MRPL42 protein abundance was consequently strongly reduced. Complex I and IV activity of the oxidative phosphorylation (OXPHOS) system were reduced and a decrease of complex I, III, IV, and mitoribosomal-related proteins was identified by proteomics. Complementation with wildtype MRPL42 corrected most of these phenotypes confirming that they were a direct consequence of the limited availability of MRPL42. Our multi-omics data confirm biallelic MRPL42 loss-of-function as the underlying cause of the fatal mitochondrial disease in our patient. Therefore, we propose MRPL42 deficiency as the cause of a mitochondrial ribosome-related combined OXPHOS- deficiency syndrome.
HostingRepository	PRIDE
AnnounceDate	2026-04-02
AnnouncementXML	Submission_2026-04-02_03:54:05.612.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Meierhofer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	timsTOF SCP

Revision	Datetime	Status	ChangeLog Entry
0	2026-01-12 19:09:11	ID requested
⏵ 1	2026-04-02 03:54:06	announced

10.1038/S41525-026-00564-1;

submitter keyword: None

Björn Fischer-Zirnsak
contact affiliation	Charité – Universitätsmedizin Berlin, Institute of Medical Genetics and Human Genetics, 13353 Berlin, Germany.
contact email	bjoern.fischer@charite.de
lab head
David Meierhofer
contact affiliation	Mass Spectrometry Facility MPIMG
contact email	meierhof@molgen.mpg.de
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/2026/04/PXD072978

PRIDE project URI

• PRIDE
  1. PXD072978
     1. Label: PRIDE project
     2. Name: A biallelic MRPL42variant causes a combined oxidative phosphorylation deficiency syndrome revealed by multi-omics