What is mitochondrial outer membrane permeabilization (MOMP)? How is it important in the process of apoptosis?

Mitochondrial outer membrane permeabilization (MOMP) is an essential and highly regulated step in the intrinsic pathway of apoptosis, which refers to the programmed and controlled death of a cell. In this process, the outer membrane of the mitochondria becomes permeable, meaning it develops openings or pores. As a result, certain proteins that are usually stored safely inside the mitochondrial intermembrane space get released into the cytoplasm. These released proteins serve as strong intracellular signals that trigger a cascade of events leading the cell towards apoptosis. Thus, MOMP acts as a critical checkpoint in deciding whether a cell will survive or enter the death pathway.

MOMP does not happen suddenly or accidentally. It is highly regulated by a group of proteins known as the Bcl-2 family. This family includes both pro-apoptotic proteins and anti-apoptotic proteins.
  • The pro-apoptotic proteins members such as BAX and BAK promote MOMP by forming pores in the outer mitochondrial membrane.
  • In contrast, the anti-apoptotic proteins like Bcl-2 and Bcl-xL try to prevent this pore formation.
When pro-apoptotic signals are stronger, BAX and BAK get activated and insert themselves into the outer membrane. They then oligomerize and form channels that allow proteins inside the mitochondria to escape into the cytoplasm. This escape marks the point where the cell becomes committed to die. Hence, MOMP is often called the "point of no return" in apoptosis.

How MOMP is important in the process of apoptosis?

Once MOMP occurs, cytochrome c is released from the intermembrane space of mitochondria. In the cytoplasm, cytochrome c binds to a protein called Apaf-1 (apoptotic protease activating factor-1). In the presence of ATP or dATP, Apaf-1 and cytochrome c form a large complex called the apoptosome. This apoptosome then activates initiator caspase-9, which further activates executioner caspases such as caspase-3 and caspase-7. These caspases begin to break down cellular components in an organized way, leading to cell death without causing inflammation.

Apart from cytochrome c, other important proteins are also released due to MOMP. SMAC/DIABLO helps by removing inhibitors of apoptosis (IAPs), allowing caspases to work more effectively. AIF (Apoptosis-inducing factor) travels to the nucleus and causes DNA fragmentation in a caspase-independent manner.

Therefore, MOMP is not just a small step in apoptosis. It is a central and irreversible stage. Once it happens, the cell cannot go back. It guarantees that the cell will follow the death pathway, either through caspases or other methods.






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