Journal
BIOPHYSICAL JOURNAL
Volume 104, Issue 2, Pages 421-431Publisher
CELL PRESS
DOI: 10.1016/j.bpj.2012.12.010
Keywords
-
Categories
Funding
- Max Planck Society
- German Cancer Research Center
- German Ministry for Education and Research (BMBF) [N.0312040]
Ask authors/readers for more resources
Based on their membrane-permeabilizing activity in vitro, it has been proposed that Bax-like proteins induce cytochrome c release during apoptosis via pore formation. However, antiapoptotic Bcl-2 proteins, which inhibit cytochrome c release, also display pore activity in model membranes. As a consequence, a unified description that aligns the pore activity of the Bcl-2 proteins with their apoptotic function is missing. Here, we studied the mechanism of membrane binding, oligomerization, and permeabilization by pro- and antiapoptotic Bcl-2 members at The single-vesicle level. We found that proapoptotic Bax forms large, stable pores via an all-or-none mechanism that can release cytochrome c. In contrast, antiapoptotic Bcl-xL induces transient permeability alterations in pure lipid membranes that have no consequences for the mitochondrial outer membrane but inhibit Bax membrane insertion. These differences in pore activity correlate with a distinct oligomeric state of Bax and Bcl-xL in membranes and can be reproduced in isolated mitochondria. Based on our findings, we propose new models for the mechanisms of action of Bax and Bcl-xL that relate their membrane activity to their opposing roles in apoptosis and beyond.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available