EVIDENCE OF A NOVEL EVENT DURING NEURONAL DEATH - DEVELOPMENT OF COMPETENCE-TO-DIE IN RESPONSE TO CYTOPLASMIC CYTOCHROME-C

Sympathetic neurons undergoing programmed cell death after nerve growt h factor (NGF) deprivation are shown to exhibit a protein synthesis-de pendent, BAX-dependent loss of cytochrome c from the mitochondria. How ever, cytoplasmic microinjection of cytochrome c was insufficient to i nduce cell death in NGF-maintained sympathetic neurons. In contrast, m icroinjection of cytochrome c rapidly induced a caspase-dependent deat h in NGF-deprived, Bax-deficient or NGF-deprived, cycloheximide-treate d neurons. Cells needed to be deprived of NGF for 15-20 hr before they acquired competence to die with injection of cytochrome c. These data suggest that NGF deprivation induced the translocation of cytochrome c and another event, which we term as competence-to-die, that was inde pendent of macromolecular synthesis and BAX function. Both these proce sses were required for neurons to undergo apoptosis.