mitochondrial outer membrane permeabilization

Definition

Target type: biologicalprocess

The process by which the mitochondrial outer membrane becomes permeable to the passing of proteins and other molecules from the intermembrane space to the cytosol as part of the apoptotic signaling pathway. [GOC:BHF, GOC:mtg_apoptosis, GOC:pg, PMID:21041309]

Mitochondrial outer membrane permeabilization (MOMP) is a crucial step in apoptosis, the programmed cell death pathway. It marks the point of no return, committing the cell to death. MOMP involves the formation of pores in the outer membrane of mitochondria, allowing the release of pro-apoptotic proteins such as cytochrome c, Smac/DIABLO, and AIF, into the cytosol.

The process is primarily regulated by the Bcl-2 family of proteins, which act as gatekeepers of MOMP. Pro-apoptotic Bcl-2 proteins, like Bax and Bak, oligomerize and insert into the outer membrane, forming the pores. Anti-apoptotic Bcl-2 proteins, like Bcl-2 and Bcl-xL, inhibit this process by binding to pro-apoptotic proteins and preventing their activation.

Several stimuli can trigger MOMP, including:

* **Intrinsic pathway**: Initiated by intracellular stress signals such as DNA damage, growth factor deprivation, or reactive oxygen species (ROS). This pathway involves the activation of pro-apoptotic proteins like Bax and Bak through a complex interplay of other proteins.
* **Extrinsic pathway**: Triggered by external signals like death receptors (e.g., TNFα receptor). This pathway activates caspase-8, which then activates Bid, a pro-apoptotic protein, leading to MOMP.

Following MOMP, cytochrome c released from the mitochondria interacts with Apaf-1 and procaspase-9 in the cytosol, leading to the formation of the apoptosome. The apoptosome activates caspase-9, triggering a cascade of caspase activation that ultimately leads to cell death.

The Smac/DIABLO and AIF released during MOMP also contribute to apoptosis by inhibiting anti-apoptotic proteins and activating caspase-independent pathways, respectively.

MOMP is tightly regulated to ensure that apoptosis occurs only when necessary and that the process is controlled. Dysregulation of MOMP can contribute to various diseases, including cancer, neurodegenerative disorders, and autoimmune diseases.'
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Proteins (3)

Compounds (13)