How do pro-apoptotic proteins differ from pro-survival proteins? Give examples (two each) for both classes of proteins mentioned

In the intrinsic pathway of apoptosis, a special group of proteins called the Bcl-2 family plays a major role in controlling whether the cell will live or die. This family has two opposite types of proteins. First type is called pro-apoptotic proteins, which promote cell death. Second type is called pro-survival proteins, which protect the cell and stop it from dying. These pro-survival proteins are also called anti-apoptotic proteins, because their function is to stop apoptosis.

These two groups work by controlling a key event called mitochondrial outer membrane permeabilization (MOMP). If pro-apoptotic proteins win, then MOMP happens and apoptosis starts. But if pro-survival proteins are stronger, then MOMP is blocked and the cell survives.

Pro-apoptotic proteins

These proteins promote apoptosis by causing damage to the outer mitochondrial membrane. They help in a critical step called mitochondrial outer membrane permeabilization (MOMP). When MOMP happens, proteins like cytochrome c, SMAC/DIABLO and AIF are released into the cytosol. This activates the caspase cascade and leads to apoptosis.

There are two types of pro-apoptotic proteins:
  1. BH3-only proteins (like BID, BIM, BAD): These are sensors of stress. They get activated by cellular damage, then go and activate the effector proteins.
  2. Effector proteins (like BAX and BAK): These directly form pores in the mitochondrial membrane. Once activated, they oligomerize (join together) and create large channels for cytochrome c to exit.

Examples of Pro-apoptotic proteins:

  • BAX: Normally present in the cytosol, but moves to mitochondria when activated. It forms pores and promotes cytochrome c release.
  • BAK: Already attached to the mitochondrial outer membrane. It undergoes conformational change during apoptosis and forms pores with BAX.

Pro-survival (anti-apoptotic) proteins

These proteins inhibit apoptosis. Their main function is to bind and neutralize the pro-apoptotic proteins. They either block BH3-only proteins or stop BAX and BAK from forming pores. Thus, they prevent MOMP and keep the mitochondria stable.

They are very important in normal cells to avoid unwanted cell death, but their overexpression is also linked to cancer.

Examples of Pro-survival (anti-apoptotic) proteins:

  • Bcl-2: It binds to activated BH3-only proteins and prevents BAX activation. This blocks the release of apoptotic factors and protects the cell.
  • Bcl-XL: Similar in function to Bcl-2, but has a stronger protective role in neurons. It binds directly to BAX or BAK and stops pore formation.






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