Format

Send to

Choose Destination
Int J Mol Sci. 2019 Aug 25;20(17). pii: E4147. doi: 10.3390/ijms20174147.

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

Author information

1
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 Nijmegen, The Netherlands.
2
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 Nijmegen, The Netherlands. g.van.den.bogaart@rug.nl.
3
Department of Molecular Immunology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, 9747 Groningen, The Netherlands. g.van.den.bogaart@rug.nl.

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.

KEYWORDS:

DNA damage; optogenetics; oxidative stress; reactive oxygen species

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center