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Citation
Lee, J.H., Budanov, A.V., Park, E.J., Birse, R., Kim, T.E., Perkins, G.A., Ocorr, K., Ellisman, M.H., Bodmer, R., Bier, E., Karin, M. (2010). Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies.  Science 327(5970): 1223--1228.
FlyBase ID
FBrf0210161
Publication Type
Research paper
Abstract
Sestrins are conserved proteins that accumulate in cells exposed to stress, potentiate adenosine monophosphate-activated protein kinase (AMPK), and inhibit activation of target of rapamycin (TOR). We show that the abundance of Drosophila sestrin (dSesn) is increased upon chronic TOR activation through accumulation of reactive oxygen species that cause activation of c-Jun amino-terminal kinase and transcription factor Forkhead box O (FoxO). Loss of dSesn resulted in age-associated pathologies including triglyceride accumulation, mitochondrial dysfunction, muscle degeneration, and cardiac malfunction, which were prevented by pharmacological activation of AMPK or inhibition of TOR. Hence, dSesn appears to be a negative feedback regulator of TOR that integrates metabolic and stress inputs and prevents pathologies caused by chronic TOR activation that may result from diminished autophagic clearance of damaged mitochondria, protein aggregates, or lipids.
PubMed ID
PubMed Central ID
PMC2866632 (PMC) (EuropePMC)
Related Publication(s)
Note
Cell biology. Burn out or fade away?
Topisirovic and Sonenberg, 2010, Science 327(5970): 1210--1211 [FBrf0214908]
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Science
    Title
    Science
    Publication Year
    1895-
    ISBN/ISSN
    0036-8075
    Data From Reference