Figure 8.

Schematic of peroxynitrite (PN) generation in isolated brain mitochondria and its activity on mitochondrial function. PN is generated when superoxide reacts with nitric oxide (NO). In isolated mitochondria, superoxide is derived from electron transport chain. There are two major mechanisms of NO generation in mitochondria. First, mitochondrial NOS (mtNOS) has been shown to produce NO (38, 39). Second, nitrosylated proteins in the mitochondria may release NO by the action of denitrosylases such as mitochondrial thioredoxin system (41, 42). Mitochondrial protein nitrosylation in turn could be induced by NO derived locally from mtNOS or NO derived extra-mitochondrially from eNOS (endothelial origin) and nNOS (neuronal origin) that diffuses through the mitochondrial membranes. SIN-1 and exogenous PN provide PN for studying the effects of PN on mitochondrial respiration. In contrast, FeTMPyP scavenges the PN and prevents its activity on mitochondrial function. Both exogenous and endogenous PN inhibit various aspects of mitochondrial respiratory function. Notably, increase in mitochondrial respiratory function in isolated mitochondria by FeTMPyP suggests intrinsic and physiological generation of PN in the mitochondria.