TY - JOUR T1 - Establishment of a Cell-Free System of Neuronal Apoptosis: Comparison of Premitochondrial, Mitochondrial, and Postmitochondrial Phases JF - The Journal of Neuroscience JO - J. Neurosci. SP - 6165 LP - 6178 DO - 10.1523/JNEUROSCI.17-16-06165.1997 VL - 17 IS - 16 AU - H. Michael Ellerby AU - Seamus J. Martin AU - Lisa M. Ellerby AU - Shahrouz S. Naiem AU - Shahrooz Rabizadeh AU - Guy S. Salvesen AU - Carlos A. Casiano AU - Neil R. Cashman AU - Douglas R. Green AU - Dale E. Bredesen Y1 - 1997/08/15 UR - http://www.jneurosci.org/content/17/16/6165.abstract N2 - Apoptosis is a fundamental process required for normal development of the nervous system and is triggered during neurodegenerative disease. To dissect the molecular events leading to neuronal cell death, we have developed a cell-free model of neuronal apoptosis. The model faithfully reproduces key elements of apoptosis, including chromatin condensation, DNA fragmentation, caspase activation/processing, and selective substrate cleavage. We report that cell-free apoptosis is activated in premitochondrial, mitochondrial, and postmitochondrial phases by tamoxifen, mastoparan, and cytochromec, respectively, allowing a functional ordering of these proapoptotic modulators. Furthermore, this is the first report of mitochondrial-mediated activation of cell-free apoptosis in a cell extract. Although Bcl-2 blocks activation at the premitochondrial and mitochondrial levels, it does not affect the postmitochondrial level. The cell-free system described here provides a valuable tool to elucidate the molecular events leading to neuronal cell death. ER -