Mitochondria act not only as a cellular powerhouse, but also play a decisive role in apoptotic and necrotic death pathways including those relevant to acute and chronic neurodegeneration (Murphy et al., J. Cerebral Blood Flow and Metabolism 19:231-245, 1999; Fiskum et al., J. Cerebral Blood Flow and Metabolism 19:351-369, 1999). The current challenge is to understand what mitochondrial events control cell death and chronic cell dysfunction, and whether therapeutic intervention is possible. Among the technologies employed at MitoKor for the discovery of disease processes and mitochondrial drug targets are the use of cellular cybrids, mitochondrial DNA sequencing, mitochondrial proteomics, in silico cloning, and targeted basic research. Recent research efforts focussed on the mechanisms of mitochondrial cytochrome c release have revealed that some apoptotic signals induce the release of cytochrome c along with another intermembrane space protein, adenylate kinase, implying a non-specific release process. However, other apoptosis inducers result in cytochrome c release in the absence of translocation of adenylate kinase. These events occurred in the absence of evidence for mitochondrial uncoupling, suggesting that the permeability transition is not responsible for apoptogen release in this model. The data further imply that multiple mechanisms exist for the release of cytochrome c from mitochondria, opening additional potential avenues for targeted drug discovery. (Supported in part by NIH NS 34154 to ANM)