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

International Journal of Molecular Sciences

Endre Laczko¹  Hubert Rehrauer¹  Reda Juskeviciene²  Margarita Brilkova²  Adrián Cortés Sanchón²  Dimitri Shcherbakov²  ErikC. Böttger² 

[1] Functional Genomics Center Zurich, ETH Zürich und Universität Zürich, 8006 Zürich, Switzerland;Institut für Medizinische Mikrobiologie, Universität Zürich, 8006 Zürich, Switzerland;

关键词: mitochondria;    misreading;    brain;    aging;    metabolome;   

DOI  :  10.3390/ijms22052746

来源: DOAJ

【 摘 要 】

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).

【 授权许可】

Unknown