| First Author | Shcherbakov D | Year | 2021 |
| Journal | Int J Mol Sci | Volume | 22 |
| Issue | 5 | PubMed ID | 33803109 |
| Mgi Jnum | J:373544 | Mgi Id | MGI:8188188 |
| Doi | 10.3390/ijms22052746 | Citation | Shcherbakov D, et al. (2021) Mitochondrial Mistranslation in Brain Provokes a Metabolic Response Which Mitigates the Age-Associated Decline in Mitochondrial Gene Expression. Int J Mol Sci 22(5) |
| abstractText | 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 Mrps5(V338Y/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). |
