Autophagy pathways activated in response to PDT contribute to cell resistance against ROS damage.
Bottom Line: Paradoxically, genetic loss of MA improved clearance of oxidized proteins and reduced photokilling.We found that up-regulation of chaperone-mediated autophagy (CMA) in unstressed Atg(-/-) cells compensated for MA loss and increased cellular resistance to PDT.These results disclose a stress-specific recruitment of autophagy pathways with cytoprotective function and unravel CMA as the dominant defence mechanism against PDT.
Affiliation: Cell Death Research and Therapy Laboratory, Department of Molecular Cell Biology, Faculty of Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.Show MeSH
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Mentions: Because induction of MA is negatively regulated by the Akt-mTOR (mammalian target of rapamycin) pathway , we investigated the impact of our ROS-based therapy on this core signalling pathway. Activation of p70S6K by phosphorylation on the mTOR-specific serine residue Thr389 and subsequent phosphorylation/activation of the p70S6K substrate S6 provides a valuable measure of mTOR activity . As soon as 1 hr after PDT, p70S6K became progressively dephosphorylated on Thr389 and phospho-S6 levels declined subsequently (Fig. 2A). Intriguingly, S6 phosphorylation level nearly recovered to control levels 16 hrs after irradiation, suggesting the modulation of S6 phosphorylation by additional p70S6K-independent mechanisms.
Affiliation: Cell Death Research and Therapy Laboratory, Department of Molecular Cell Biology, Faculty of Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.