Phototoxic effects of lysosome-associated genetically encoded photosensitizer killer red

Ekaterina O. Serebrovskaya, Alina P. Ryumina, Maria E. Boulina, Marina V. Shirmanova, Elena V. Zagaynova, Ekaterina A. Bogdanova, Sergey A. Lukyanov, Konstantin A. Lukyanov

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

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 surfaceof 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

Original languageEnglish
Article number071403
JournalJournal of Biomedical Optics
Volume19
Issue number7
DOIs
Publication statusPublished - Jul 2014
Externally publishedYes

Keywords

  • cell death
  • fluorescence microscopy
  • green fluorescent protein
  • photosensitizer
  • phototoxicity

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