The cytosolic domain of Bcl-2 forms small pores in model mitochondrial outer membrane after acidic pH-induced membrane association / 生物医学工程学杂志
Journal of Biomedical Engineering
;
(6): 130-137, 2009.
Artigo
em Inglês
| WPRIM
| ID: wpr-280248
ABSTRACT
The permeability of mitochondrial outer membrane (MOM) is regulated by the proteins of the Bcl-2 family via their interactions at the membrane. While pro-apoptotic Bax protein promotes MOM permeabilization (MOMP) releasing cytochrome c after activation by BH3-only protein, anti-apoptotic Bcl-2 protein protects MOM. However both Bax and Bcl-2 can form pores in model membranes. Unlike Bax pore that has been extensively studied and reported to be directly linked to MOMP, Bcl-2 pore is much less known; thus we investigated the pore-forming property of recombinant Bcl-2 lacking the C-terminal transmembrane sequence (Bcl-2deltaTM) in liposomal membranes of MOM lipids. We found that (1) Bcl-2 formed pores at acidic pH that induced the association of Bcl-2 with liposome; (2) Bcl-2 pore size was dependent on Bcl-2 concentration, suggesting that oligomerization is involved in Bcl-2 pore formation; (3) Unlike Bax pore that could release large molecules up to 2 mega-Da, Bcl-2 pore was smaller and could only release the molecules of a few kilo-Da. Therefore, Bcl-2 and Bax may form different size pores in MOM, and while the large pore formed by Bax may release cytochrome c during apoptosis, the small pore formed by Bcl-2 may maintain the normal MOM permeability.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Permeabilidade da Membrana Celular
/
Grupo dos Citocromos c
/
Proteínas de Transporte da Membrana Mitocondrial
/
Membranas Mitocondriais
/
Proteína X Associada a bcl-2
/
Proteína bcl-X
/
Proteína Agonista de Morte Celular de Domínio Interatuante com BH3
/
Concentração de Íons de Hidrogênio
/
Lipossomos
/
Metabolismo
Limite:
Humanos
Idioma:
Inglês
Revista:
Journal of Biomedical Engineering
Ano de publicação:
2009
Tipo de documento:
Artigo
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