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@ARTICLE{Gioran:140583,
      author       = {Gioran, Anna and Piazzesi, Antonia and Bertan, Fabio and
                      Schroer, Jonas and Wischhof, Lena and Nicotera, Pierluigi
                      and Bano, Daniele},
      title        = {{M}ulti-omics identify xanthine as a pro-survival
                      metabolite for nematodes with mitochondrial dysfunction.},
      journal      = {The EMBO journal},
      volume       = {38},
      number       = {6},
      issn         = {0261-4189},
      address      = {Hoboken, NJ [u.a.]},
      publisher    = {Wiley},
      reportid     = {DZNE-2020-06905},
      pages        = {e99558},
      year         = {2019},
      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 favors 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 downstream metabolic output of IIS inhibition.
                      We provide evidence that supplementation of FDA-approved
                      xanthine derivatives is sufficient to promote fitness and
                      survival of nematodes carrying mitochondrial lesions.
                      Together, our data describe previously unknown molecular
                      components of a metabolic network that can extend the
                      lifespan of short-lived mitochondrial mutant animals.},
      keywords     = {Adenosine Triphosphate: metabolism / Animals /
                      Caenorhabditis elegans: drug effects / Caenorhabditis
                      elegans: growth $\&$ development / Caenorhabditis elegans:
                      metabolism / Caenorhabditis elegans Proteins: genetics /
                      Caenorhabditis elegans Proteins: metabolism / Insulin:
                      chemistry / Insulin-Like Growth Factor I: antagonists $\&$
                      inhibitors / Longevity / Metabolome / Mitochondria: drug
                      effects / Mitochondria: metabolism / Mitochondria: pathology
                      / Mitochondrial Diseases: metabolism / Mitochondrial
                      Diseases: pathology / Mitochondrial Diseases: prevention
                      $\&$ control / Proteome / Transcriptome / Xanthine:
                      administration $\&$ dosage / Xanthine: metabolism /
                      Caenorhabditis elegans Proteins (NLM Chemicals) / Insulin
                      (NLM Chemicals) / Proteome (NLM Chemicals) / Xanthine (NLM
                      Chemicals) / Insulin-Like Growth Factor I (NLM Chemicals) /
                      Adenosine Triphosphate (NLM Chemicals)},
      cin          = {AG Bano / AG Nicotera},
      ddc          = {570},
      cid          = {I:(DE-2719)1013003 / I:(DE-2719)5000018},
      pnm          = {341 - Molecular Signaling (POF3-341) / 342 - Disease
                      Mechanisms and Model Systems (POF3-342)},
      pid          = {G:(DE-HGF)POF3-341 / G:(DE-HGF)POF3-342},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30796049},
      pmc          = {pmc:PMC6418696},
      doi          = {10.15252/embj.201899558},
      url          = {https://pub.dzne.de/record/140583},
}