Mitochondrial NOS upregulation during renal I/R causes apoptosis in a peroxynitrite-dependent manner

In the last decade, various groups have found evidence of nitric oxide production by mitochondrial nitric oxide synthase (mNOS) in a range of experimental models. However, little is known about the role of mNOS in renal ischemia–reperfusion (I/R) injury and its possible involvement in the apoptotic pathway. We analyzed the role of mNOS in apoptosis promotion in rat kidney I/R and its direct implication through experiments in which isolated kidney mitochondria were subjected to hypoxia/reoxygenation. Results showed that neuronal NOS located in the inner mitochondrial membrane is upregulated during renal I/R and that this upregulation, together with the increase in nitric oxide production, is involved in the generation of intramitochondrial peroxynitrite, which in turn leads to cytochrome c release and apoptosis induction in renal I/R.