Rapamycin increases mitochondrial efficiency by mtDNA-dependent reprogramming of mitochondrial metabolism in Drosophila.

ABSTRACT: Downregulation of the mammalian target of rapamycin (mTOR) pathway by its inhibitor rapamycin is emerging as a potential pharmacological intervention that mimics the beneficial effects of dietary restriction. Modulation of mTOR has diverse effects on mitochondrial metabolism and biogenesis, but the role of the mitochondrial genotype in mediating these effects remains unknown. Here, we use novel mitochondrial genome replacement strains in Drosophila to test the hypothesis that genes encoded in mitochondrial DNA (mtDNA) influence the mTOR pathway. We show that rapamycin increases mitochondrial respiration and succinate dehydrogenase activity, decreases H2O2 production and generates distinct shifts in the metabolite profiles of isolated mitochondria versus whole Drosophila. These effects are

SUBMITTER: Villa-Cuesta E 

PROVIDER: S-EPMC4021473 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature