Mitochondrial mistranslation in brain provokes a metabolic response which mitigates the age-associated decline in mitochondrial gene expression
- Journal Article
Rights / licenseCreative Commons Attribution 4.0 International
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
Journal / seriesInternational Journal of Molecular Sciences
Pages / Article No.
SubjectMitochondria; Misreading; Brain; Aging; Metabolome
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