|
|
|
|
|
|
|
||
© The Rockefeller University Press,
0021-9525/2003/7/245 $5.00
The Journal of Cell Biology, Volume 162, Number 2, 245-256
Article |
Alternating metabolic pathways in NGF-deprived sympathetic neurons affect caspase-independent death
Address correspondence to Eugene M. Johnson, Washington University School of Medicine, 660 South Euclid Ave., Box 8103, Saint Louis, MO 63110. Tel.: (314) 362-3926. Fax: (314) 747-1772. E-mail: ejohnson{at}pcg.wustl.edu
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.
Key Words: apoptosis; cytochrome c; mitochondria; permeability transition pore; programmed cell death
m, mitochondrial membrane potential; PTP, permeability transition pore; ROS, reactive oxygen species; VDAC, voltage-dependent anion channel.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
