Rapamycin rescues mitochondrial myopathy via coordinated activation of autophagy and lysosomal biogenesis

The mTOR inhibitor rapamycin ameliorates the clinical and biochemical phenotype of mouse, worm, and cellular models of mitochondrial disease, via an unclear mechanism. Here, we show that prolonged rapamycin treatment improved motor endurance, corrected morphological abnormalities of muscle, and increased cytochrome c oxidase (COX) activity of a muscle-specific Cox15 knockout mouse (Cox15sm/sm ). Rapamycin treatment restored autophagic flux,...