Reduced TORC1 signaling abolishes mitochondrial dysfunctions and shortened chronological lifespan of Isc1p-deficient cells.

ABSTRACT: The target of rapamycin (TOR) is an important signaling pathway on a hierarchical network of interacting pathways regulating central biological processes, such as cell growth, stress response and aging. Several lines of evidence suggest a functional link between TOR signaling and sphingolipid metabolism. Here, we report that the TORC1-Sch9p pathway is activated in cells lacking Isc1p, the yeast orthologue of mammalian neutral sphingomyelinase 2. The deletion of TOR1 or SCH9 abolishes the premature aging, oxidative stress sensitivity and mitochondrial dysfunctions displayed by isc1Δ cells and this is correlated with the suppression of the autophagic flux defect exhibited by the mutant strain. The protective effect of TOR1 deletion, as opposed to that of SCH9</

SUBMITTER: Teixeira V 

PROVIDER: S-EPMC5349163 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature