BAX, BAK, and BOK: A Coming of Age for the BCL-2 Family Effector Proteins.

ABSTRACT: The BCL-2 family of proteins control a key checkpoint in apoptosis, that of mitochondrial outer membrane permeabilization or, simply, mitochondrial poration. The family consists of three subgroups: BH3-only initiators that respond to apoptotic stimuli; antiapoptotic guardians that protect against cell death; and the membrane permeabilizing effectors BAX, BAK, and BOK. On activation, effector proteins are converted from inert monomers into membrane permeabilizing oligomers. For many years, this process has been poorly understood at the molecular level, but a number of recent advances have provided important insights. We review the regulation of these effectors, their activation, subsequent conformational changes, and the ensuing oligomerization events that enable mitochondrial poration, which initiates apoptosis through release of key signaling factors such as cytochrome c We highlight the mysteries that remain in understanding these important proteins in an endeavor to provide a comprehensive picture of where the field currently sits and where it is moving toward.

SUBMITTER: Moldoveanu T 

PROVIDER: S-EPMC7111251 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature