Radical Stress Is More Cytotoxic in the Nucleus than in Other Organelles

Laurent M. Paardekooper, Ellen van Vroonhoven, Martin Ter Beest, Geert van den Bogaart*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

13 Citations (Scopus)
160 Downloads (Pure)

Abstract

Cells are exposed to reactive oxygen species (ROS) as a by-product of mitochondrial metabolism, especially under hypoxia. ROS are also enzymatically generated at the plasma membrane during inflammation. Radicals cause cellular damage leading to cell death, as they react indiscriminately with surrounding lipids, proteins, and nucleotides. However, ROS are also important for many physiological processes, including signaling, pathogen killing and chemotaxis. The sensitivity of cells to ROS therefore likely depends on the subcellular location of ROS production, but how this affects cell viability is poorly understood. As ROS generation consumes oxygen, and hypoxia-mediated signaling upregulates expression of antioxidant transcription factor Nrf2, it is difficult to discern hypoxic from radical stress. In this study, we developed an optogenetic toolbox for organelle-specific generation of ROS using the photosensitizer protein SuperNova which produces superoxide anion upon excitation with 590 nm light. We fused SuperNova to organelle specific localization signals to induce ROS with high precision. Selective ROS production did not affect cell viability in most organelles except for the nucleus. SuperNova is a promising tool to induce locally targeted ROS production, opening up new possibilities to investigate processes and organelles that are affected by localized ROS production.

Original languageEnglish
Article number4147
Number of pages11
JournalInternational Journal of Molecular Sciences
Volume20
Issue number17
DOIs
Publication statusPublished - 25-Aug-2019

Keywords

  • reactive oxygen species
  • oxidative stress
  • optogenetics
  • DNA damage
  • REACTIVE OXYGEN
  • CROSS-PRESENTATION
  • MITOCHONDRIAL ROS
  • REDOX REGULATION
  • NADPH OXIDASE
  • CYTOCHROME-C
  • TRAFFICKING
  • AUTOPHAGY
  • REQUIRES
  • SITES

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