FIG. 7.

Summary of proposed mechanisms by which neuronal antioxidant state influences cytochrome c release in NGF-deprived sympathetic neurons. Withdrawal of NGF causes an increase in Bax-dependent O₂^·− production by mitochondria. The O₂^·− dismutates to H₂O₂ in a reaction catalyzed primarily by SOD2 (MnSOD), the mitochondrial matrix form of superoxide dismutase. The H₂O₂ then serves as a signal causing cytochrome c to exit the intermembrane space and enter the cytoplasm. Readdition of NGF rapidly activates glutathione redox cycling, lowering ROS, and blocking further cytochrome c release.