FIG. 7.

S-NO targets and mitochondrial function. Nitric oxide (NO^·) can mediate protein S-nitrosation (-S-NO) or activate soluble guanylyl cyclase to foster cGMP-mediated kinase function. Protein –S-NO has been shown to occur in response to physiological and pathological production of NO^· (463), and NO^· has been shown to regulate mitochondrial function through several mechanisms. Complex I S-nitrosation has been associated with diminished activity; however, conflicting results exist as to whether it inhibits or promotes mitochondrial ROS generation (57, 98, 108). Similarly, S-nitrosation of complex IV has been suggested to inhibit mitochondrial respiration (97, 474). In general, low concentrations of NO^· are associated with antiapoptotic mechanisms, perhaps, in part, via the inhibition of caspase 3 activation or the decreased degradation of the antiapoptotic Bcl-2 following their respective S-nitrosation (21, 424). Nitric oxide may enhance cell death and mitochondrial fragmentation in neurodegenerative diseases by its effects on dynamin-related protein-1 (Drp1), which promotes mitochondrial fission (86). There is some controversy, however, as to whether these are cGMP-kinase-mediated or –S-NO-specific effects (45). In addition, in myogenesis, NO^· has the opposite effect on mitochondrial fission, promoting the fusion of mitochondria into an elongated network by inhibiting Drp1-mediated fission (113).