The role of mitochondria in epilepsy: implications for neurodegenerative diseases.

The epileptic seizures observed in a broad variety of diseases involving mitochondrial DNA (mtDNA) and central nervous system pathology strongly suggest the possible role of mitochondria in the pathomechanism of various forms of epilepsy. The mtDNA mutations in these diseases affect the functions of complexes of oxidative phosphorylation that have mitochondria-encoded subunits. Similar deficiencies of oxidative phosphorylation, in particular of Complexes I and IV, have been detected in the epileptogenic brain regions of therapy-resistant focal epilepsies, such as the hippocampal subfield CA3 in temporal lobe epilepsy with Ammon's horn sclerosis.

Characterization of superoxide-producing sites in isolated brain mitochondria.

Mitochondrial respiratory chain complexes I and III have been shown to produce superoxide but the exact contribution and localization of individual sites have remained unclear. We approached this question investigating the effects of oxygen, substrates, inhibitors, and of the NAD+/NADH redox couple on H2O2 and superoxide production of isolated mitochondria from rat and human brain. Although rat brain mitochondria in the presence of glutamate+malate alone do generate only small amounts of H2O2 (0.