Surveillance-activated defenses block the ROS-induced mitochondrial unfolded protein response
14.03.2013
Runkel ED, Liu S, Baumeister R, Schulze E.
PLoS Genet. 2013;9(3):e1003346
Cellular respiration takes place in the mitochondria. Reactive oxygen species (ROS) are a damaging byproduct of cellular respiration. At adverse conditions, when the load of ROS becomes critical for mitochondrial function, a stress response pathway, the unfolded protein response of the mitochondria (UPRmt) is triggered. This can be monitored by the activation of the hsp 6 gene. We used the model organism Caenorhabditis elegans to screen for genes required for the activation of hsp 6 and found 54 novel candidates. Surprisingly, most of the genes we identified serve basic cellular functions and are no plausible candidates for regulatory functions. However, this group of genes was recently shown to trigger a cellular surveillance mediated stress response, sensing pathogen invasion and toxin attack, and forcing the animals to escape from environmental hazards. This mechanism partially requires signaling through the kinase KGB 1. In worms, in which KGB 1 was inactivated, UPRmt was not longer interrupted by downregulation of the cellular surveillance activating genes. We suggest this surveillance system as a regulator of the UPRmt that prevents its activation when pathogen attack is sensed.
