The permeability transition pore triggers Bax translocation to mitochondria during neuronal apoptosis
| Autor: | Kim A. Heidenreich, T A Precht, Shoshona S. Le, Ron J. Bouchard, Daniel A. Linseman, Tracey A. Laessig, Brent D. Butts, Reid A. Phelps |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Caspase 3
Apoptosis Mitochondrial Membrane Transport Proteins Culture Media Serum-Free Ion Channels Rats Sprague-Dawley chemistry.chemical_compound Mitochondrial membrane transport protein Bcl-2-associated X protein Cerebellum Proto-Oncogene Proteins Animals Humans Point Mutation Molecular Biology Cells Cultured bcl-2-Associated X Protein Neurons biology Bcl-2-Like Protein 11 Mitochondrial Permeability Transition Pore Cytochrome c MPTP Intrinsic apoptosis Cytochromes c Membrane Proteins Cell Biology Caspase 9 Cell biology Mitochondria Rats Enzyme Activation Protein Transport nervous system Mitochondrial permeability transition pore chemistry Proto-Oncogene Proteins c-bcl-2 Caspases biology.protein Cyclosporine Potassium Apoptosis Regulatory Proteins Carrier Proteins |
| Zdroj: | Cell death and differentiation. 12(3) |
| ISSN: | 1350-9047 |
| Popis: | Cerebellar granule neurons (CGNs) require depolarization for their survival in culture. When deprived of this stimulus, CGNs die via an intrinsic apoptotic cascade involving Bim induction, Bax translocation, cytochrome c release, and caspase-9 and -3 activation. Opening of the mitochondrial permeability transition pore (mPTP) is an early event during intrinsic apoptosis; however, the precise role of mPTP opening in neuronal apoptosis is presently unclear. Here, we show that mPTP opening acts as an initiating event to stimulate Bax translocation to mitochondria. A C-terminal (alpha9 helix) GFP-Bax point mutant (T182A) that constitutively localizes to mitochondria circumvents the requirement for mPTP opening and is entirely sufficient to induce CGN apoptosis. Collectively, these data indicate that the major role of mPTP opening in CGN apoptosis is to trigger Bax translocation to mitochondria, ultimately leading to cytochrome c release and caspase activation. |
| Databáze: | OpenAIRE |
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