mTor Is a Signaling Hub in Cell Survival: A Mass-Spectrometry-Based Proteomics Investigation

mTor plays a central role in controlling
protein homeostasis and
cell survival. Recently, we have demonstrated that perturbations of
mTor signaling are implicated in Alzheimer’s disease (AD) and
that mTor complex 1 (mTorC1) is involved in the formation of toxic
phospho-tau. Therefore, we employed mass-spectrometry-based proteomics
to identify specific protein expression changes in relation with cell
survival in human neuroblastoma SH-SY5Y cells expressing genetically
modified mTor. Cell death in SH-SY5Y cells was induced by moderate
serum deprivation. Using flow cytometry we observed that up-regulated
mTor complex 2 (mTorC2) increases the number of viable cells. By using
a combination approach of proteomic and enrichment analysis we have
identified several proteins (Thioredoxin-dependent peroxide reductase,
Peroxiredoxin-5, Cofilin 1 (non-muscle), Annexin A5, Mortalin, and
14-3-3 protein zeta/delta) involved in mitochondrial integrity, apoptotosis,
and pro-survival functions (caspase inhibitor activity and anti-apoptosis)
that were significantly altered by mTor activity modulation. The major
findings of this study are the implication of mTorC2 but not mTorC1
in cell viability modulation by activating the pro-survival machinery.
Taken together, these results suggest that up-regulated mTorC2 might
be playing an important role in promoting cell survival by suppressing
the mitochondria-caspase-apoptotic pathway in vitro.