Serine- and threonine/valine-dependent activation of PDK and Tor orthologs converge on Sch9 to promote aging

Mario Giuseppe Mirisola, Giusi Taormina, Min Wei, Paola Fabrizio, Jia Hu, Valter D. Longo

Risultato della ricerca: Articlepeer review

51 Citazioni (Scopus)

Abstract

Dietary restriction extends longevity in organisms ranging from bacteria to mice and protects primates from a variety ofdiseases, but the contribution of each dietary component to aging is poorly understood. Here we demonstrate that glucose and specific amino acids promote stress sensitization and aging through the differential activation of the Ras/cAMP/PKA,PKH1/2 and Tor/S6K pathways. Whereas glucose sensitized cells through a Ras-dependent mechanism, threonine and valine promoted cellular sensitization and aging primarily by activating the Tor/S6K pathway and serine promoted sensitization viaPDK1 orthologs Pkh1/2. Serine, threonine and valine activated a signaling network in which Sch9 integrates TORC1 and Pkhsignaling via phosphorylation of threonines 570 and 737 and promoted intracellular relocalization and transcriptional inhibition of the stress resistance protein kinase Rim15. Because of the conserved pro-aging role of nutrient and growth signaling pathways in higher eukaryotes, these results raise the possibility that similar mechanisms contribute to aging inmammals.
Lingua originaleEnglish
Numero di pagine13
RivistaPLoS Genetics
Volume10
Stato di pubblicazionePublished - 2014

All Science Journal Classification (ASJC) codes

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  • ???subjectarea.asjc.1300.1312???
  • ???subjectarea.asjc.1300.1311???
  • ???subjectarea.asjc.2700.2716???
  • ???subjectarea.asjc.1300.1306???

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