Alternating metabolic pathways in NGF-deprived sympathetic neurons affect caspase-independent death

Louis K. Chang, Robert E. Schmidt, Eugene M. Johnson

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Mitochondrial release of cytochrome c in apoptotic cells activates caspases, which execute apoptotic cell death. However, the events themselves that culminate in caspase activation can have deleterious effects because caspase inhibitor-saved cells ultimately die in a caspase-independent manner. To determine what events may underlie this form of cell death, we examined bioenergetic changes in sympathetic neurons deprived of NGF in the presence of a broad-spectrum caspase inhibitor, boc-aspartyl -(OMe)-fluoromethylketone. Here, we report that NGF-deprived, boc-aspartyl-(OMe)-fluoromethylketone-saved neurons rely heavily on glycolysis for ATP generation and for survival. Second, the activity of F0F1 contributes to caspase-independent death, but has only a minor role in the maintenance of mitochondrial membrane potential, which is maintained primarily by electron transport. Third, permeability transition pore inhibition by cyclosporin A attenuates NGF deprivation-induced loss of mitochondrial proteins, suggesting that permeability transition pore opening may have a function in regulating the degradation of mitochondria after cytochrome c release. Identification of changes in caspase inhibitor-saved cells may provide the basis for rational strategies to augment the effectiveness of the therapeutic use of postmitochondrial interventions.

Original languageEnglish
Pages (from-to)245-256
Number of pages12
JournalJournal of Cell Biology
Issue number2
StatePublished - Jul 21 2003


  • Apoptosis
  • Cytochrome c
  • Mitochondria
  • Permeability transition pore
  • Programmed cell death


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