Activation of the intrinsic apoptosis pathway is regulated by members of the BCL2 protein family. The BH3-only pro-apoptotic proteins (colored yellow) bind to and neutralize their pro-survival relatives (colored pink), thereby unleashing the pro-apoptotic effectors BAX and BAK (colored red) to permeabilize the mitochondrial outer membrane. Some BH3-only proteins may also engage BAX and BAK directly. Mitochondrial cytochrome c is released into the cytoplasm, triggering assembly of an APAF1 complex that activates caspase-9. The executioner caspases 3 and 7 are cleaved and activated by caspase-9 resulting in the highly orchestrated proteolytic events that dismantle the cell. Deubiquitinases, including USP9X, DUB3, and USP13, promote cell survival by cleaving K48-linked polyubiquitin from MCL-1 that would otherwise target it for proteasomal degradation. The pro-apoptotic effector BOK is unstable owing to its constitutive ubiquitination. A DUB that removes ubiquitin from BOK has not been described. Figure created with BioRender.com.