We previously reported that a low level of lysosomal photoda mage can markedly promote the subsequent efficacy of PDT directed at mitochondria. This involves release of Ca2+ from photo damaged lysosomes, cleavage of the autophagy-associated protein ATG5 after activation of calpain and an interaction between the ATG5 fragment and mitochondria resulting in enhanced apoptosis. Inhibition of calpain activity abolished th is effect. We examined permissible irradiation sequences. Lysosomal photodamage must occur first with the ‘enhancement’ effect showing a short half-life (~ 15 min), presumably reflecting the survival of the ATG5 fragment. Simultaneous photo damage to both loci was found to be as effective as the sequential protocol. Since Photofrin can target both lysosomes and mitochondria for photo damage, this broad spectrum of photo damage may explain the efficacy of this photo sensitizing agent in spite of a sub-optimal absorbance profile at a sub- optimal wavelength for tissue transparency.
David Kessel, "Sequential vs. simultaneous photokilling by mitochondrial and lysosomal photodamage," Proc. SPIE 10047, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVI, 1004702 (Presented at SPIE BiOS: January 28, 2017; Published: 8 February 2017); https://doi.org/10.1117/12.2251207.
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