Rapamycin activates autophagy and lysosomal biogenesis in a mitochondrial myopathy model

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 (Cox15sm/sm). Rapamycin treatment restored autophagic flux, which was impaired in naïve Cox15sm/sm muscle, and reduced the number of damaged mitochondria, which accumulated in untreated Cox15sm/sm mice. Conversely, rilmenidine, an mTORC1-independent autophagy inducer, was ineffective on the myopathic features of Cox15sm/sm animals. This stark difference supports the idea that inhibition of mTORC1 by rapamycin has

SUBMITTER: Prof. Massimo Zeviani 

PROVIDER: S-SCDT-EMM-2017-08799 | biostudies-other |

REPOSITORIES: biostudies-other