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Phototoxic effects of lysosome-associated genetically encoded photosensitizer KillerRed

Ekaterina O Serebrovskaya1, Alina P Ryumina1, Maria E Boulina1

  • 1Russian Academy of Sciences, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997, Moscow, Russia.

Journal of Biomedical Optics
|December 25, 2013
PubMed

Insights

KillerRed protein targeted to lysosomes induces cell death upon light exposure. This optogenetic tool can trigger necrosis or apoptosis, offering control over cell fate.

Area of Science:

  • Cell Biology
  • Optogenetics
  • Photodynamic Therapy

Background:

  • KillerRed is a phototoxic fluorescent protein inducing oxidative stress via light.
  • Previous studies localized KillerRed to mitochondria and plasma membranes for cell death induction.

Purpose of the Study:

  • To investigate the phototoxicity of KillerRed fused with Rab7, targeting lysosomes.
  • To determine the cell death pathways (apoptosis vs. necrosis) induced by lysosome-localized KillerRed.

Main Methods:

  • Constructing a KillerRed-Rab7 fusion protein for lysosomal targeting.
  • Illuminating cells with green-orange light to activate KillerRed.
  • Assessing cell viability, membrane integrity, and nuclear morphology.
  • Utilizing inhibitory analysis of lysosomal cathepsins.

Main Results:

  • Lysosome-associated KillerRed (KillerRed-Rab7) induced efficient light-triggered cell death.
  • Lysosomal cathepsins were found to be crucial for KillerRed-Rab7 phototoxicity.
  • Cell death occurred via necrosis at high light intensity and apoptosis at lower intensities.

Conclusions:

  • KillerRed-Rab7 is an effective optogenetic tool for inducing cell death.
  • The protein allows for tunable induction of necrosis or apoptosis based on light intensity.
  • This offers potential applications in targeted cell population control.

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