期刊
FEBS JOURNAL
卷 285, 期 3, 页码 416-431出版社
WILEY
DOI: 10.1111/febs.14186
关键词
apoptosis; BAK; BAX; BCL-2 family; DRP1; mitochondria; mitochondrial outer membrane permeabilization
资金
- European Research Council [ERC-2012-StG 309966]
- Deutsche Forschungsgemeinschaft [FOR 2036]
- University of Tubingen
Bax and Bak are members of the Bcl-2 family and core regulators of the intrinsic pathway of apoptosis. Upon apoptotic stimuli, they are activated and oligomerize at the mitochondrial outer membrane (MOM) to mediate its permeabilization, which is considered a key step in apoptosis. However, the molecular mechanism underlying Bax and Bak function has remained a key question in the field. Here, we review recent structural and biophysical evidence that has changed our understanding of how Bax and Bak promote MOM permeabilization. We also discuss how the spatial regulation of Bcl-2 family preference for binding partners contributes to regulate Bax and Bak activation. Finally, we consider the contribution of mitochondrial composition, dynamics and interaction with other organelles to apoptosis commitment. A new perspective is emerging, in which the control of apoptosis by Bax and Bak goes beyond them and is highly influenced by additional mitochondrial components.
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