Figure 3. Schematic diagram. NO plays a dual regulatory role in PGC-1 expression. Short-term increases of NO concentration down-regulate of PGC-1 via PKG and, sustained, elevated, NO concentrations up-regulates PGC-1. Reduced PGC-1 expression decreases the mitochondrial detoxification capacity, and therefore increases the mitochondrial production of ROS. Elevated ROS could play a role in the induction of PGC-1 and the mitochondrial oxidative stress protection system that results from sustained, elevated, NO production.