The permeability transition pore triggers Bax translocation to mitochondria during neuronal apoptosis.
Cell Death Differ
; 12(3): 255-65, 2005 Mar.
Article
em En
| MEDLINE
| ID: mdl-15637643
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Apoptose
/
Proteínas Proto-Oncogênicas c-bcl-2
/
Canais Iônicos
/
Mitocôndrias
/
Neurônios
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article