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

ABSTRACT: 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 (Cox15^sm/sm ). Rapamycin treatment restored autophagic flux, which was impaired in naïve Cox15^sm/sm muscle, and reduced the number of damaged mitochondria, which accumulated in untreated Cox15^sm/sm mice. Conversely, rilmenidine, an mTORC1-independent autophagy inducer, was ineffective on the myopathic features o

SUBMITTER: Civiletto G 

PROVIDER: S-EPMC6220341 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature