Mitochondrial mistranslation in brain provokes a metabolic response which mitigates the age-associated decline in mitochondrial gene expression
Abstract
Mitochondrial misreading, conferred by mutation V338Y in mitoribosomal protein Mrps5, in-vivo 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 mitigates 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). Show more
Permanent link
https://doi.org/10.3929/ethz-b-000474390Publication status
publishedExternal links
Journal / series
International Journal of Molecular SciencesVolume
Pages / Article No.
Publisher
MDPI AGSubject
Mitochondria; Misreading; Brain; Aging; MetabolomeOrganisational unit
02207 - Functional Genomics Center Zurich / Functional Genomics Center Zurich
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