Mutation in MRPS34 compromises protein synthesis and causes mitochondrial dysfunction

Tara Richman, Judith Ermer, Stefan Davies, Kara Perks, Helena Viola, Anne-Marie Shearwood, Livia Hool, Oliver Rackham, Aleksandra Filipovska

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37 Citations (Scopus)
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Abstract

© 2015 Richman et al. The evolutionary divergence of mitochondrial ribosomes from their bacterial and cytoplasmic ancestors has resulted in reduced RNA content and the acquisition of mitochondria-specific proteins. The mitochondrial ribosomal protein of the small subunit 34 (MRPS34) is a mitochondria-specific ribosomal protein found only in chordates, whose function we investigated in mice carrying a homozygous mutation in the nuclear gene encoding this protein. The Mrps34 mutation causes a significant decrease of this protein, which we show is required for the stability of the 12S rRNA, the small ribosomal subunit and actively translating ribosomes. The synthesis of all 13 mitochondrially-encoded polypeptides is compromised in the mutant mice, resulting in reduced levels of mitochondrial proteins and complexes, which leads to decreased oxygen consumption and respiratory complex activity. The Mrps34 mutation causes tissue-specific molecular changes that result in heterogeneous pathology involving alterations in fractional shortening of the heart and pronounced liver dysfunction that is exacerbated with age. The defects in mitochondrial protein synthesis in the mutant mice are caused by destabilization of the small ribosomal subunit that affects the stability of the mitochondrial ribosome with age.
Original languageEnglish
Article numbere1005089
Pages (from-to)e1005089
Number of pages22
JournalPLoS Genetics
Volume11
Issue number3
DOIs
Publication statusPublished - 27 Mar 2015

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