Multi-omics identify xanthine as a pro-survival metabolite for nematodes with mitochondrial dysfunction

ABSTRACT: Aberrant mitochondrial function contributes to the pathogenesis of various metabolic and chronic disorders. Inhibition of insulin/IGF-1 signaling (IIS) represents a promising avenue for the treatment of mitochondrial diseases, although many of the molecular mechanisms underlying this beneficial effect remain elusive. Using an unbiased multi-omics approach, we report here that IIS inhibition reduces protein synthesis and favours catabolism in mitochondrial deficient Caenorhabditis elegans. We unveil that the lifespan extension does not occur through the restoration of mitochondrial respiration, but as a consequence of an ATP-saving metabolic rewiring that is associated with an evolutionarily conserved phosphoproteome landscape. Furthermore, we identify xanthine accumulation as a prominent d

SUBMITTER: Dr. Anna Gioran 

PROVIDER: S-SCDT-EMBOJ-2018-99558 | biostudies-other |

REPOSITORIES: biostudies-other