MCL-1 has a number of functions and features that make it unique among the anti-apoptotic BCL-2 family members.3
- MCL-1 is essential for early embryogenesis as well as the development and maintenance of lymphocytes, neurons, synovial fibroblasts, and hematopoietic stem cells.3
The balance between pro- and anti-apoptotic BCL-2 family proteins occurs at the mitochondrion where the effectors of apoptosis, BAK and BAX promote mitochondrial outer membrane permeabilization (MOMP) and apoptotic cell death when activated by BH3-only activators like BIM, BID, and PUMA.2
- Anti-apoptotic proteins (BCL-2, MCL-1, BCL-XL, and BCL-W) derail this process by sequestering the effector and activator proteins and preventing activation of mitochondrial outer membrane permeabilization (MOMP).2
MCL-1 dimerizes with pro-apoptotic proteins, such as BAK or BAX on the mitochondrial membrane and sequesters pro-apoptotic proteins in a similar fashion as other pro-survival molecules, such as BCL-2 or BCL-XL, to prevent MOMP.4
The anti-apoptotic proteins (e.g., BCL-XL, BCL-2, MCL-1) inhibit both the activator BH3-only proteins and the pore-forming effector proteins by mutual sequestration (T’d arrows). The sensitizer BH3-only proteins (e.g., BAD, NOXA) bind to and inhibit the anti-apoptotic proteins also by mutual sequestration.