A redox sensor as a potential regulator of ROS signaling in C. elegans

Abstract

The ability of an organism to maintain redox homeostasis is critical for its survival. At the cellular level, exposure to oxidative insult can irreversibly damage DNA, proteins, and lipids, all of which can lead to cell apoptosis or necrosis. To counteract such oxidative insults, organisms have developed the ability to sense and respond to oxidative stress, termed the oxidative stress response. SKN-1 is the major transcription factor that coordinates the C. elegans oxidative stress response. Our lab has recently demonstrated that, in C. elegans, intestinal infections stimulate the production of reactive oxygen species (ROS) by Ce-Duox1/BLI-3. While this response has protective effects, it challenges the host¿s intracellular redox homeostasis, resulting in the simultaneous up-regulation of intracellular detoxification enzymes. This response occurs through the activation of SKN-1, in a p38 MAPK pathway dependent manner. However, it is still currently unknown how BLI-3-generated ROS is capable of activating SKN-1. This question is of broad interest because ROS can serve as an important signaling molecule not only in the immune response, but in the regulation of other vital processes such as cell growth and differentiation. We propose that activation of the SKN-1 is regulated by a redox sensor, which is sensitive to the ROS generated by BLI-3.