*2.6. Analysis of Mitochondrial Function in Biopsies*

Skeletal muscle homogenate (5%, w/v) was prepared from fresh tissue by using a glass-Teflon homogenizer in a medium containing 150 mM KCl, 50 mM Tris-HCl, 2 mM EDTA, pH 7.4, and 0.2 ug/mL Aprotinin at 4 ◦C. Mitochondria were isolated from the homogenate by differential centrifugation as described elsewhere [24]. Heart tissue homogenates (7%, w/v) were prepared from −80 ◦C stored frozen samples of left and right heart ventricles in 0.32 M sucrose, 10 mM Tris-HCl, 1 mM EDTA, pH 7.4, and 1μg/mL PIC (protease inhibitor mixture Sigma P8340) using glass-Teflon and glass-glass Dounce homogenizers. The subsequent methods are described in detail in Supplementary Materials. A western blot analysis of mitochondrial proteins, measurement of mitochondrial DNA content, measurement of activities of respiratory chain complexes and citrate synthase [25], high resolution oxygraphy, and measurement of the content of total coenzyme Q10 were described previously in details and in the Supplementary Materials.

#### **3. Results**
