Fig. 2. Mitochondrial oxidative/nitrosative stress and dysfunction. Excessive NAPQI in the mitochondria combines with ATP synthase, GSH synthase, and oxidative respiratory chain enzymes to form protein adducts, which subsequently lead to mitochondrial dysfunction and oxidative stress. NAPQI-ATP synthase hinders ATP synthesis and gradually triggers the opening of MPT pores. The abnormality of MPT pores is exacerbated by the inhibition of ATP synthesis. NAPQI-GSH synthase reduces GSH synthesis, weakens the excretion of NAPQI, and induces the formation of ROS. ROS can be eliminated by the antioxidant enzyme system, but excessive ROS combine with free NO to form peroxynitrite, causing mitochondrial DNA damage. NAPQI: N-acetyl-p-benzoquinone imine; ADP: adenosine diphosphate; ATP: adenosine triphosphate; GSH: glutathione; ROS: reactive oxygen species; MPT: membrane permeability transition; NO: nitric oxide.