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J Biomed Opt. 2014 Jul;19(7):071403. doi: 10.1117/1.JBO.19.7.071403.

Phototoxic effects of lysosome-associated genetically encoded photosensitizer KillerRed.

Author information

1
Russian Academy of Sciences, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997, Moscow, Russia.
2
Nizhny Novgorod State Medical Academy, 603005 Minin Sq., 10/1, 603005, Nizhny Novgorod, Russia.
3
Russian Academy of Sciences, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997, Moscow, RussiabNizhny Novgorod State Medical Academy, 603005 Minin Sq., 10/1, 603005, Nizhny Novgorod, Russia.

Abstract

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. Time-lapse 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.

PMID:
24365992
DOI:
10.1117/1.JBO.19.7.071403
[Indexed for MEDLINE]
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