Bax, but not Bcl-x(L), decreases the lifetime of planar phospholipid bilayer membranes at subnanomolar concentrations

Citation
G. Basanez et al., Bax, but not Bcl-x(L), decreases the lifetime of planar phospholipid bilayer membranes at subnanomolar concentrations, P NAS US, 96(10), 1999, pp. 5492-5497
Citations number
35
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN journal
00278424 → ACNP
Volume
96
Issue
10
Year of publication
1999
Pages
5492 - 5497
Database
ISI
SICI code
0027-8424(19990511)96:10<5492:BBNBDT>2.0.ZU;2-7
Abstract
Release of proteins through the outer mitochondrial membrane can be a criti cal step in apoptosis, and the localization of apoptosis-regulating Bcl-2 f amily members there suggests they control this process. We used planar phos pholipid membranes to test the effect of full-length Bax and Bcl-x(L) synth esized in vitro and native Bax purified from bovine thymocytes. Instead of forming pores with reproducible conductance levels expected for ionic chann els, Bax, but not Bcl-xL, created arbitrary and continuously variable chang es in membrane permeability and decreased the stability of the membrane, re gardless of whether the source of the protein was synthetic or native, This breakdown of the membrane permeability barrier and destabilization of the bilayer was quantified by using membrane lifetime measurements. Bax decreas ed membrane lifetime in a voltage- and concentration-dependent manner. Bcl- x(L) did not protect against Bax-induced membrane destabilization, supporti ng the idea that these two proteins function independently. Corresponding t o a physical theory for lipidic pore formation, Bax potently diminished the linear tension of the membrane (i.e., the energy required to form the edge of a new pore). We suggest that Bax acts directly by destabilizing the lip id bilayer structure of the outer mitochondrial membrane, promoting the for mation of a pore-the apoptotic pore-large enough to allow mitochondrial pro teins such as cytochrome c to be released into the cytosol, Bax could then enter and permeabilize the inner mitochondrial membrane through the same ho le.