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Open AccessArticle

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

1
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 Nijmegen, The Netherlands
2
Department of Molecular Immunology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, 9747 Groningen, The Netherlands
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(17), 4147; https://doi.org/10.3390/ijms20174147
Received: 31 July 2019 / Revised: 21 August 2019 / Accepted: 23 August 2019 / Published: 25 August 2019
(This article belongs to the Special Issue Adaptation to Hypoxia: A Chimera?)
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. View Full-Text
Keywords: reactive oxygen species; oxidative stress; optogenetics; DNA damage reactive oxygen species; oxidative stress; optogenetics; DNA damage
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MDPI and ACS Style

Paardekooper, L.M.; van Vroonhoven, E.; ter Beest, M.; van den Bogaart, G. Radical Stress Is More Cytotoxic in the Nucleus than in Other Organelles. Int. J. Mol. Sci. 2019, 20, 4147.

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