PXD062317

PXD062317 is an original dataset announced via ProteomeXchange.

Title	Further delineation of defects in MRPS2 causing human OXPHOS deficiency and early developmental abnormalities in zebrafish
Description	Background: Mitochondrial ribosomal protein-small 2 (MRPS2) encodes a vital structural protein essential for assembling mitochondrial ribosomal small subunit and thus mitochondrial translation. We describe individuals with phenotypes of acute onset severe metabolic decompensation and symptomatic hypoglycemia. Exome sequencing identified a biallelic variant in MRPS2 in an affected individual: c.490G>A p.(Glu164Lys). Methods: We performed proteomics analysis of patient-derived fibroblasts along with control samples. Proteins derived from cultured fibroblast lysates were digested with trypsin and labeled with tandem mass tags (TMT). Pooled TMT-labeled peptides were fractionated by basic pH reversed-phase liquid chromatography (bRPLC) on a C18 column and twenty-four fractions were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) for total proteomics. Results: Proteomics analysis revealed decreased levels of MRPS2 protein in patient-derived fibroblasts in comparison with controls. A similar decrease was observed in levels of mitochondrial proteins NADH-ubiquinone oxidoreductase 75 kDa subunit (NDUFS1), and cytochrome c oxidase subunit 4 (COX4). Furthermore, all of the detected small mitochondrial ribosomal subunit components were found to be decreased and most large mitochondrial ribosomal subunit proteins were increased. Conclusions: Our data reveal that in a patient with a biallelic variant in MRPS2 (c.490G>A p.(Glu164Lys)), the levels of the encoded protein are significantly decreased. Our findings of altered levels of both large and small mitochondrial ribosomal subunit proteins likely indicate overall changes in mitochondrial ribosomal component synthesis and assembly in association with decreased availability of MRPS2.
HostingRepository	PRIDE
AnnounceDate	2025-11-10
AnnouncementXML	Submission_2025-11-09_17:09:44.701.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Akhilesh Pandey
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Ascend

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-27 09:55:22	ID requested
⏵ 1	2025-11-09 17:09:45	announced

10.1038/s41431-025-01858-1;

Kandettu A, Yeole M, Sekar H, Garapati K, Kaur N, Anand A, Hegde P, Nair K, Medishetti R, Bhat V, Radhakrishnan P, Mundkur SC, Shrikiran HA, Pandey A, Sevilimedu A, Chakrabarty S, Shukla A, Further delineation of defects in MRPS2 causing human OXPHOS deficiency and early developmental abnormalities in zebrafish. Eur J Hum Genet, 33(11):1451-1461(2025) [pubmed]

submitter keyword: mitochondrial disorder, rare disease,genetic disorder

Akhilesh Pandey, M.D., Ph.D.
contact affiliation	Department of Laboratory Medicine and Pathology Mayo Clinic Rochester, Minnesota 55905 United States
contact email	pandey.akhilesh@mayo.edu
lab head
Akhilesh Pandey
contact affiliation	Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905
contact email	pandey.akhilesh@mayo.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD062317
     1. Label: PRIDE project
     2. Name: Further delineation of defects in MRPS2 causing human OXPHOS deficiency and early developmental abnormalities in zebrafish