Bax and Bak function as the outer membrane component of the mitochondrial permeability pore in regulating necrotic cell death in mice.
Elife
; 2: e00772, 2013 Aug 27.
Article
em En
| MEDLINE
| ID: mdl-23991283
ABSTRACT
A critical event in ischemia-based cell death is the opening of the mitochondrial permeability transition pore (MPTP). However, the molecular identity of the components of the MPTP remains unknown. Here, we determined that the Bcl-2 family members Bax and Bak, which are central regulators of apoptotic cell death, are also required for mitochondrial pore-dependent necrotic cell death by facilitating outer membrane permeability of the MPTP. Loss of Bax/Bak reduced outer mitochondrial membrane permeability and conductance without altering inner membrane MPTP function, resulting in resistance to mitochondrial calcium overload and necrotic cell death. Reconstitution with mutants of Bax that cannot oligomerize and form apoptotic pores, but still enhance outer membrane permeability, permitted MPTP-dependent mitochondrial swelling and restored necrotic cell death. Our data predict that the MPTP is an inner membrane regulated process, although in the absence of Bax/Bak the outer membrane resists swelling and prevents organelle rupture to prevent cell death. DOIhttp//dx.doi.org/10.7554/eLife.00772.001.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte da Membrana Mitocondrial
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Proteína X Associada a bcl-2
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Proteína Killer-Antagonista Homóloga a bcl-2
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Necrose
Limite:
Animals
Idioma:
En
Revista:
Elife
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos