title: Mutation in MRPS34 compromises protein synthesis and causes mitochondrial dysfunction.
abstract: 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.
authors: Harry Perkins Institute of Medical Research, Centre for Medical Research, QEII Medical Centre, The University of Western Australia, Nedlands, Western Australia, Australia.
authors: Tara R
authors: TR
authors: Richman
authors: Harry Perkins Institute of Medical Research, Centre for Medical Research, QEII Medical Centre, The University of Western Australia, Nedlands, Western Australia, Australia.
authors: Judith A
authors: JA
authors: Ermer
authors: Harry Perkins Institute of Medical Research, Centre for Medical Research, QEII Medical Centre, The University of Western Australia, Nedlands, Western Australia, Australia.
authors: Stefan M K
authors: SM
authors: Davies
authors: Harry Perkins Institute of Medical Research, Centre for Medical Research, QEII Medical Centre, The University of Western Australia, Nedlands, Western Australia, Australia.
authors: Kara L
authors: KL
authors: Perks
authors: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, Western Australia, Australia; Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia.
authors: Helena M
authors: HM
authors: Viola
authors: Harry Perkins Institute of Medical Research, Centre for Medical Research, QEII Medical Centre, The University of Western Australia, Nedlands, Western Australia, Australia.
authors: Anne-Marie J
authors: AM
authors: Shearwood
authors: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, Western Australia, Australia; Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia.
authors: Livia C
authors: LC
authors: Hool
authors: Harry Perkins Institute of Medical Research, Centre for Medical Research, QEII Medical Centre, The University of Western Australia, Nedlands, Western Australia, Australia; School of Chemistry and Biochemistry, The University of Western Australia, Crawley, Western Australia, Australia.
authors: Oliver
authors: O
authors: Rackham
authors: Harry Perkins Institute of Medical Research, Centre for Medical Research, QEII Medical Centre, The University of Western Australia, Nedlands, Western Australia, Australia; School of Chemistry and Biochemistry, The University of Western Australia, Crawley, Western Australia, Australia.
authors: Aleksandra
authors: A
authors: Filipovska
mesh_terms: D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics; D004734:Energy Metabolism; D006330:Heart Defects, Congenital / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008107:Liver Diseases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics*; D000069396:Mitochondrial Ribosomes / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D012335:RNA, Ribosomal / Q000235:genetics; D012269:Ribosomal Proteins / Q000096:biosynthesis* / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; C471039:MRPS34 protein, human; C000603730:MRPS34 protein, mouse; D024101:Mitochondrial Proteins; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; D012269:Ribosomal Proteins