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Mitochondrial Mistranslation in Brain Provokes a Metabolic Response Which Mitigates the Age-Associated Decline in Mitochondrial Gene Expression

Dimitri Shcherbakov, Reda Juskeviciene, A Corés Sanchón, Margarita Brilkova, Hubert Rehrauer, Endre Laczko, E C Böttger
2021

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Mitochondrial misreading, conferred by mutation V338Y in mitoribosomal protein Mrps5, invivo is associated with a subtle neurological phenotype. Brain mitochondria of homozygous knock-in mutant Mrps5V338Y/V338Y mice show decreased oxygen consumption and reduced ATP levels. Using a combination of unbiased RNA-Seq with untargeted metabolomics, we here demonstrate a concerted response, which alleviates the impaired functionality of OXPHOS complexes in Mrps5 mutant mice. This concerted response
more » ... gates the age-associated decline in mitochondrial gene expression and compensates for impaired respiration by transcriptional upregulation of OXPHOS components together with anaplerotic replenishment of the TCA cycle (pyruvate, 2-ketoglutarate). Citation: Shcherbakov, D.; Juskeviciene, R.; Cortés Sanchón, A.; Brilkova, M.; Rehrauer, H.; Laczko, E.; Böttger, E.C. Mitochondrial Mistranslation in Brain Provokes a Metabolic Response Which Mitigates the Age-Associated Decline in
doi:10.5167/uzh-201295 fatcat:c3pal4yh65ayjgnokbtqxxcu7y
Citation

Dimitri Shcherbakov, Reda Juskeviciene, A Corés Sanchón, Margarita Brilkova, Hubert Rehrauer, Endre Laczko, E C Böttger. "Mitochondrial Mistranslation in Brain Provokes a Metabolic Response Which Mitigates the Age-Associated Decline in Mitochondrial Gene Expression." (2021)