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
Related in: MedlinePlus
Mentions: CMA has been shown to be involved in the selective removal of oxidized proteins in cells treated with H2O2 or the superoxide-generating drug paraquat . Because activation of CMA after cellular stress is associated with a redistribution of CMA-active lysosomes from the cytosol towards the perinuclear region [16, 40], we evaluated the involvement of this lysosomal pathway by immunofluorescence microscopy. While untreated cells displayed a homogenous pattern of LAMP2A, the specific receptor for CMA, in the cytosol, PDT induced a marked redistribution of LAMP2A positive puncta to the perinuclear region of 3T3 cells (Fig. 6A) and MEFs (Fig. 6C). PDT induced also the relocalization of the CMA chaperone Hsc70 towards the perinuclear area (Fig. 6A), thus suggesting the recruitment of the CMA machinery in photosensitized cells. Moreover, a fraction of the total pool of LAMP2A positive lysosomes co-localized with Hsc70, thus indicating CMA activation by PDT in MA-competent cells (Fig. 6B).
Affiliation: Cell Death Research and Therapy Laboratory, Department of Molecular Cell Biology, Faculty of Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.