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: We then hypothesized that if up-regulation of CMA in Atg5-deficient cells was responsible for their increased resistance towards PDT and efficient clearance of oxidized proteins (Fig. 5A), LAMP2A-deficient CMA-incompetent cells  would be highly sensitized to PDT. Consistent with this, LAMP2A deficiency accelerated the pattern of caspase 3 activation and PARP cleavage, correlating with a persistent pattern of protein carbonylation (Fig. 7A, C and E) and resulting in a significant sensitization of these cells to PDT-induced cell death within a wide range of PDT doses (Fig. 7D). Because LAMP2A-deficient cells were extremely vulnerable to PDT, we used a milder dose (i.e. reduced hypericin concentration and light dose) to evaluate apoptotic parameters, which is reflected by a reduced pattern of protein carbonylation, caspase 3 processing and cell death in these fibroblasts as compared to MEFs (Fig. 7A, C–E).
Affiliation: Cell Death Research and Therapy Laboratory, Department of Molecular Cell Biology, Faculty of Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.