Mitochondrial mutations alter endurance exercise response and determinants in mice

RNA Sequencing of skeletal muscle and heart of mice with distinct mitochondrial mutations revealed a differential transcriptomic response to endurance exercise training and altered determinants of exercise capacity and response. We studied five mouse strains with distinct mitochondrial mutations on the C57BL/6Eij (Nnt+/+) background. Control B6 mice, ND5 mice (ND5 m.12352C>T, ND5S204F), ND6 mice (ND6 m.13997G>A, ND6P25L), CO1 mice (CO1m.6589T>C , CO1V421A) and ANT1 mice (ANT1, Slc25a4-/-). Mice were exercise trained (50% of maximal running capacity, every 2nd day, 45min, for a total of 8 weeks) or non-exercised, exercise capacity was tested prior and following that time period and mice were sacrificed (cervical dislocation) 6 days after the last training session. The soleus muscle and heart were flash frozen and RNASeq was performed. Differential gene expression and GSEA between strains and between exercised and non-exercised for each strain was performed. In addition, expression data of every mouse were correlated to the exercise capacity (running time and VO2max) and exercise response ( delta running time and delta VO2max). For heart, RNASeq was correlated to ejection fraction of every mouse measured by echocardiography.