This failure is likely attributable to deletion of HHF2, which results in reduced starvation resistance (Davey et al., 2012) and is associated with reduced lifespan (Feser et al., 2010).
Expression of PI3K DA led to reduced starvation resistance (Fig. 4A), reduced levels of stored TAGs and their mobilization upon starvation, as compared with itpr ku (Fig. 4C).
These results suggest that reduced starvation resistance in the absence of dSir2 expression is caused by an inability to mobilize energy reserves.
HHF2 deletions, but not HHF1 deletions, cause reduced starvation resistance (Davey et al. Environ Microbiol 2012, PMID 22356628), which is consistent with the HHF2 deletion in the H4S47C mutant strain causing the phenotypic syndrome that we observe in this strain.
This phenotypic syndrome is likely attributable to the replacement of the two histone H4 genes, HHF1 and HHF2 with a single mutant HHF1 gene, resulting in reduced H4 dosage: Deleting HHF2 causes reduced starvation resistance (Davey et al., 2012 ), and partial histone depletion in general is associated with reduced longevity (Feser et al., 2010 ).
Expression of other known modulators and effectors of insulin signaling, such as a transgene for dominant negative JNK (UASBsk DN; Wang et al., 2005) in the IPCs and an RNAi construct for Thor (Baker and Thummel, 2007) in the fat body, also reduced starvation resistance in itpr ku (supplementary material Fig. S5A,B).
The transgenic expression of Bcl-2 in mouse myocardial cells reduced starvation-induced autophagy.
Complete deletion of ATG31 or ATG8 in control strains severely reduced starvation-induced phosphatase activity as expected.
NSC185058 reduced starvation-enhanced protein degradation by more than 50%, while NSC377071 proved more effective, comparable to 3MA.
