Phototoxic effects of lysosome-associated genetically encoded photosensitizer KillerRed.

Autor: Serebrovskaya, Ekaterina O., Ryumina, Alina P., Boulina, Maria E., Shirmanov, Marina V., Zagaynov, Elena V., Bogdanova, Ekaterina A., Lukyanov, Sergey A., Lukyanov, Konstantin A.
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Zdroj: Journal of Biomedical Optics; Jul2014, Vol. 19 Issue 7, p1-4, 4p
Abstrakt: KillerRed is a unique phototoxic red fluorescent protein that can be used to induce local oxidative stress by green-orange light illumination. Here we studied phototoxicity of KillerRed targeted to cytoplasmic surface of lysosomes via fusion with Rab7, a small GTPase that is known to be attached to membranes of late endosomes and lysosomes. It was found that lysosome-associated KillerRed ensures efficient light-induced cell death similar to previously reported mitochondria- and plasma membrane--localized KillerRed. Inhibitory analysis demonstrated that lysosomal cathepsins play an important role in the manifestation of KillerRed-Rab7 phototoxicity. Timelapse monitoring of cell morphology, membrane integrity, and nuclei shape allowed us to conclude that KillerRed-Rab7-mediated cell death occurs via necrosis at high light intensity or via apoptosis at lower light intensity. Potentially, KillerRed-Rab7 can be used as an optogenetic tool to direct target cell populations to either apoptosis or necrosis. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index