The cytosolic domain of Bcl-2 forms small pores in model mitochondrial outer membrane after acidic pH-induced membrane association.
- Author:
Jun PENG
1
;
Suzanne M LAPOLLA
;
Zhi ZHANG
;
Jialing LIN
Author Information
1. Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Boulevard, Oklahoma City, OK 73190, USA. junlab@hotmail.com
- Publication Type:Journal Article
- MeSH:
BH3 Interacting Domain Death Agonist Protein;
metabolism;
Cell Membrane Permeability;
Cytochrome c Group;
metabolism;
Humans;
Hydrogen-Ion Concentration;
Liposomes;
metabolism;
Mitochondrial Membrane Transport Proteins;
metabolism;
Mitochondrial Membranes;
metabolism;
bcl-2-Associated X Protein;
metabolism;
bcl-X Protein;
metabolism
- From:
Journal of Biomedical Engineering
2009;26(1):130-137
- CountryChina
- Language:English
-
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.
