Dataset Information

Further delineation of defects in MRPS2 causing human OXPHOS deficiency and early developmental abnormalities in zebrafish

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Fibroblast

DISEASE(S): Genetic Disease

SUBMITTER: Akhilesh Pandey

LAB HEAD: Akhilesh Pandey, M.D., Ph.D.

PROVIDER: PXD062317 | Pride | 2025-11-10

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	MRPS2_TMTPro_8Plex_F1-24_Proteins.xlsx	Xlsx
	MRPS2_TMTpro_8plex_F1-24_Peptides.xlsx	Xlsx
	MRPS2_TMTpro_8plex_F1.raw	Raw
	MRPS2_TMTpro_8plex_F10.raw	Raw
	MRPS2_TMTpro_8plex_F11.raw	Raw

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Publications

Further delineation of defects in MRPS2 causing human OXPHOS deficiency and early developmental abnormalities in zebrafish.

Kandettu Amoolya A Yeole Mayuri M Sekar Hamsini H Garapati Kishore K Kaur Namanpreet N Anand Aakanksha A Hegde Pranavi P Nair Karthik K Medishetti Raghavender R Bhat Vivekananda V Radhakrishnan Periyasamy P Mundkur Suneel C SC Shrikiran Hebbar A HA Pandey Akhilesh A Sevilimedu Aarti A Chakrabarty Sanjiban S Shukla Anju A

European journal of human genetics : EJHG 20250513 11

Mitochondrial ribosomal protein-small 2 (MRPS2) encodes a vital structural protein essential for assembling mitoribosomal small subunit and thus mitochondrial translation. Any defect in mitochondrial translation impacts OXPHOS activity and cellular respiration. Defects in MRPS2 have been implicated recently in four families with combined oxidative phosphorylation deficiency-36 (MIM# 617950). We herein describe two individuals from two unrelated families with variable phenotypes of acute onset se ...[more]

PMID: 40360742

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