6 research outputs found
Chemical genetic screen identifies lithocholic acid as an anti-aging compound that extends yeast chronological life span in a TOR-independent manner, by modulating housekeeping longevity assurance processes
In
chronologically aging yeast, longevity can be extended by administering a
caloric restriction (CR) diet or some small molecules. These life-extending
interventions target the adaptable target of rapamycin (TOR) and
cAMP/protein kinase A (cAMP/PKA) signaling pathways that are under the
stringent control of calorie availability. We designed a chemical genetic
screen for small molecules that increase the chronological life span of
yeast under CR by targeting lipid metabolism and modulating housekeeping
longevity pathways that regulate longevity irrespective of the number of
available calories. Our screen identifies lithocholic acid (LCA) as one of
such molecules. We reveal two mechanisms underlying
the life-extending effect of LCA in chronologically aging yeast. One
mechanism operates in a calorie availability-independent fashion and
involves the LCA-governed modulation of housekeeping longevity assurance
pathways that do not overlap with the adaptable TOR and cAMP/PKA pathways.
The other mechanism extends yeast longevity under non-CR conditions and
consists in LCA-driven unmasking of the previously unknown anti-aging
potential of PKA. We provide evidence that LCA modulates housekeeping
longevity assurance pathways by suppressing lipid-induced necrosis,
attenuating mitochondrial fragmentation, altering oxidation-reduction
processes in mitochondria, enhancing resistance to oxidative and thermal
stresses, suppressing mitochondria-controlled apoptosis, and enhancing
stability of nuclear and mitochondrial DNA
Chemical genetic screen identifies lithocholic acid as an anti-aging compound that extends yeast chronological life span in a TOR-independent manner, by modulating housekeeping longevity assurance processes
In chronologically aging yeast, longevity can be extended by administering a caloric restriction (CR) diet or some small molecules. These life-extending interventions target the adaptable target of rapamycin (TOR) and cAMP/protein kinase A (cAMP/PKA) signaling pathways that are under the stringent control of calorie availability. We designed a chemical genetic screen for small molecules that increase the chronological life span of yeast under CR by targeting lipid metabolism and modulating housekeeping longevity pathways that regulate longevity irrespective of the number of available calories. Our screen identifies lithocholic acid (LCA) as one of such molecules. We reveal two mechanisms underlying the life-extending effect of LCA in chronologically aging yeast. One mechanism operates in a calorie availability-independent fashion and involves the LCA-governed modulation of housekeeping longevity assurance pathways that do not overlap with the adaptable TOR and cAMP/PKA pathways. The other mechanism extends yeast longevity under non-CR conditions and consists in LCA-driven unmasking of the previously unknown anti-aging potential of PKA. We provide evidence that LCA modulates housekeeping longevity assurance pathways by suppressing lipid-induced necrosis, attenuating mitochondrial fragmentation, altering oxidation-reduction processes in mitochondria, enhancing resistance to oxidative and thermal stresses, suppressing mitochondria-controlled apoptosis, and enhancing stability of nuclear and mitochondrial DNA
Expression of the Salmonella Spp. Virulence Factor SifA in Yeast Alters Rho1 Activity on Peroxisomes
SifA is a virulence protein required for assembly and tubulation of a modified phagosome that promotes Salmonella replication. We show that SifA expressed in yeast induces membrane invagination during peroxisome proliferation and requires functional Rho1p. This is consistent with SifA ability to interact with RhoA and the fact that it is a GEF structural homologue