When activated, the proapoptotic protein Bax permeabilizes the mitochondrial outer membrane, allowing the release of proteins into the cytosol and thus initiating the execution phase of apoptosis. When activated Bax was reconstituted into phospholipid membranes, we discovered a new, to our knowledge, property of Bax channels: voltage gating. We also found that the same Bax sample under the same experimental conditions could give rise to two radically different channels: Type A, which is small, well behaved, homogeneous, and voltage-gated, and Type B, which is large, noisy, and voltage-independent. One Type B channel can be converted irreversibly into a population of Type A channels by the addition of La3+. This conversion process appears to involve a two-dimensional budding mechanism. The existence of these two types of Bax channels suggests a process for controlling the degree of mitochondrial outer membrane permeabilization.
Bibliographical noteFunding Information:
This work was supported by a grant from the National Science Foundation (MCB-1023008).