Defective mitochondrial homeostasis and protein synthesis in icKO hearts. A, Gene Ontology analysis of mitochondrial homeostasis–related biology process changes. B, Heatmap of mitochondrial aminoacyl-tRNA synthetase (mtARS) genes of inducible cardiac-specific Fars2 knockout (icKO) compared with wild-type (WT) mice from RNA sequencing analysis. C, Top, aminoacylation assay for mitochondrial mt-tRNAPhe in mouse heart. Charged (Phe-mt-tRNAPhe) and uncharged tRNA (mt-tRNAPhe) are indicated. Bottom, quantification of Phe-mt-tRNAPhe/mt-tRNAPhe from the top panel (n=3). D, Western blots of oxidative phosphorylation (OXPHOS) complexes and Fars2 in WT and icKO mice. E, Quantification of the OXPHOS complexes from D (n=3). F and G, Expression levels of mitochondrial DNA (mtDNA) coding genes in the heart of icKO mice at 3 weeks (F) and icKO mice at 10 weeks (G; n=3 mice per group). *P<0.05; **P<0.01; ***P<0.001.
|