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Here, we recapitulate the suggested A1555G\u2010mediated pathomechanism in an experimental model of mitoribosomal mistranslation by directed mutagenesis of mitoribosomal protein MRPS5. We first establish that the ratio of cysteine\/methionine incorporation and read\u2010through of mtDNA\u2010encoded MT\u2010CO1 protein constitute reliable measures of mitoribosomal misreading. Next, we demonstrate that human HEK293 cells expressing mutant V336Y MRPS5 show increased mitoribosomal mistranslation. As for immortalized lymphocytes of individuals with the pathogenic A1555G mutation, we find little changes in the transcriptome of mutant V336Y MRPS5 HEK cells, except for a coordinated upregulation of transcripts for cytoplasmic ribosomal proteins. Homozygous knock\u2010in mutant\n                    <jats:italic>Mrps5<\/jats:italic>\n                    V338Y mice show impaired mitochondrial function and a phenotype composed of enhanced susceptibility to noise\u2010induced hearing damage and anxiety\u2010related behavioral alterations. The experimental data in V338Y mutant mice point to a key role of mitochondrial translation and function in stress\u2010related behavioral and physiological adaptations.\n                  <\/jats:p>","DOI":"10.15252\/embr.201846193","type":"journal-article","created":{"date-parts":[[2018,9,20]],"date-time":"2018-09-20T09:12:32Z","timestamp":1537434752000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Mutant MRPS5 affects mitoribosomal accuracy and confers stress\u2010related behavioral alterations"],"prefix":"10.1038","volume":"19","author":[{"given":"Rashid","family":"Akbergenov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Duscha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann\u2010Kristina","family":"Fritz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reda","family":"Juskeviciene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Oishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Schmitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitri","family":"Shcherbakov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youjin","family":"Teo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heithem","family":"Boukari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Freihofer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Isnard\u2010Petit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Oettinghaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Frank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kader","family":"Thiam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubert","family":"Rehrauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6172-5422","authenticated-orcid":false,"given":"Eric","family":"Westhof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Schacht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Eckert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Wolfer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2570-0121","authenticated-orcid":false,"given":"Erik C","family":"B\u00f6ttger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,9,20]]},"reference":[{"key":"BFEMBR201846193_CR1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S1567-7249(00)00002-7","volume":"1","author":"IE Scheffler","year":"2001","unstructured":"Scheffler IE (2001) A century of mitochondrial research: achievements and perspectives. 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