Home > Publications Database > Multi-omics identify xanthine as a pro-survival metabolite for nematodes with mitochondrial dysfunction. > print

001     140583
005     20240619121039.0
024 7 _ |a 10.15252/embj.201899558
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024 7 _ |a pmid:30796049
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024 7 _ |a pmc:PMC6418696
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024 7 _ |a 0261-4189
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024 7 _ |a 1460-2075
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037 _ _ |a DZNE-2020-06905
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Gioran, Anna
|0 P:(DE-2719)2810464
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245 _ _ |a Multi-omics identify xanthine as a pro-survival metabolite for nematodes with mitochondrial dysfunction.
260 _ _ |a Hoboken, NJ [u.a.]
|c 2019
|b Wiley
264 _ 1 |3 online
|2 Crossref
|b EMBO
|c 2019-02-22
264 _ 1 |3 print
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|b EMBO
|c 2019-03-15
336 7 _ |a article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a 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.
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542 _ _ |i 2019-02-22
|2 Crossref
|u http://creativecommons.org/licenses/by/4.0/
542 _ _ |i 2019-02-22
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650 _ 7 |a Caenorhabditis elegans Proteins
|2 NLM Chemicals
650 _ 7 |a Insulin
|2 NLM Chemicals
650 _ 7 |a Proteome
|2 NLM Chemicals
650 _ 7 |a Xanthine
|0 1AVZ07U9S7
|2 NLM Chemicals
650 _ 7 |a Insulin-Like Growth Factor I
|0 67763-96-6
|2 NLM Chemicals
650 _ 7 |a Adenosine Triphosphate
|0 8L70Q75FXE
|2 NLM Chemicals
650 _ 2 |a Adenosine Triphosphate: metabolism
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Caenorhabditis elegans: drug effects
|2 MeSH
650 _ 2 |a Caenorhabditis elegans: growth & development
|2 MeSH
650 _ 2 |a Caenorhabditis elegans: metabolism
|2 MeSH
650 _ 2 |a Caenorhabditis elegans Proteins: genetics
|2 MeSH
650 _ 2 |a Caenorhabditis elegans Proteins: metabolism
|2 MeSH
650 _ 2 |a Insulin: chemistry
|2 MeSH
650 _ 2 |a Insulin-Like Growth Factor I: antagonists & inhibitors
|2 MeSH
650 _ 2 |a Longevity
|2 MeSH
650 _ 2 |a Metabolome
|2 MeSH
650 _ 2 |a Mitochondria: drug effects
|2 MeSH
650 _ 2 |a Mitochondria: metabolism
|2 MeSH
650 _ 2 |a Mitochondria: pathology
|2 MeSH
650 _ 2 |a Mitochondrial Diseases: metabolism
|2 MeSH
650 _ 2 |a Mitochondrial Diseases: pathology
|2 MeSH
650 _ 2 |a Mitochondrial Diseases: prevention & control
|2 MeSH
650 _ 2 |a Proteome
|2 MeSH
650 _ 2 |a Transcriptome
|2 MeSH
650 _ 2 |a Xanthine: administration & dosage
|2 MeSH
650 _ 2 |a Xanthine: metabolism
|2 MeSH
700 1 _ |a Piazzesi, Antonia
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700 1 _ |a Bertan, Fabio
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700 1 _ |a Schroer, Jonas
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700 1 _ |a Wischhof, Lena
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700 1 _ |a Nicotera, Pierluigi
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700 1 _ |a Bano, Daniele
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773 1 8 |a 10.15252/embj.201899558
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773 _ _ |a 10.15252/embj.201899558
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