Evidence of a novel event during neuronal death: development of competence-to-die in response to cytoplasmic cytochrome c

Neuron. 1998 Oct;21(4):695-705. doi: 10.1016/s0896-6273(00)80587-5.


Sympathetic neurons undergoing programmed cell death after nerve growth factor (NGF) deprivation are shown to exhibit a protein synthesis-dependent, BAX-dependent loss of cytochrome c from the mitochondria. However, cytoplasmic microinjection of cytochrome c was insufficient to induce cell death in NGF-maintained sympathetic neurons. In contrast, microinjection of cytochrome c rapidly induced a caspase-dependent death in NGF-deprived, Bax-deficient or NGF-deprived, cycloheximide-treated 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 independent of macromolecular synthesis and BAX function. Both these processes were required for neurons to undergo apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Animals
  • Caspases / physiology
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cells, Cultured
  • Cycloheximide / pharmacology
  • Cytochrome c Group / metabolism
  • Cytochrome c Group / pharmacology*
  • Cytoplasm / physiology*
  • Dose-Response Relationship, Drug
  • Mice
  • Microinjections
  • Mitochondria / metabolism
  • Nerve Growth Factors / deficiency
  • Nerve Growth Factors / pharmacology
  • Nerve Tissue Proteins / biosynthesis
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / physiology*
  • Protein Synthesis Inhibitors / pharmacology
  • Proto-Oncogene Proteins / deficiency
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2*
  • Superior Cervical Ganglion / cytology
  • bcl-2-Associated X Protein


  • Amino Acid Chloromethyl Ketones
  • Bax protein, mouse
  • Cytochrome c Group
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Protein Synthesis Inhibitors
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • butyloxycarbonyl-O-methyl-aspartyl-fluoromethyl ketone
  • Cycloheximide
  • Caspases