apoptosome assembly

Definition

Target type: biologicalprocess

The aggregation, arrangement and bonding together of the apoptosome, a multisubunit protein complex involved in the signaling phase of the apoptotic process. [GOC:mtg_apoptosis]

Apoptosome assembly is a crucial step in the intrinsic apoptotic pathway, a programmed cell death mechanism essential for development and maintaining tissue homeostasis. The process involves the sequential recruitment and activation of key proteins, ultimately leading to the activation of caspase-9 and the execution of the apoptotic cascade.

1. **Cytochrome c Release:** Upon cellular stress, mitochondria release cytochrome c into the cytosol. This release is triggered by various stimuli, including DNA damage, growth factor deprivation, and reactive oxygen species.

2. **Apaf-1 Activation:** Cytochrome c binds to the apoptotic protease activating factor 1 (Apaf-1), a protein that exists as an inactive monomer in the cytosol. This binding promotes Apaf-1 oligomerization, forming a wheel-like structure known as the apoptosome.

3. **Caspase-9 Recruitment:** The apoptosome acts as a platform for caspase-9 recruitment. Caspase-9, a pro-apoptotic caspase, binds to the Apaf-1 oligomer via its CARD (caspase activation and recruitment domain).

4. **Caspase-9 Activation:** The apoptosome brings multiple caspase-9 molecules together, facilitating their auto-activation. This auto-activation involves a conformational change that allows caspase-9 to become an active protease.

5. **Caspase Cascade Activation:** Active caspase-9 then cleaves and activates downstream executioner caspases, such as caspase-3 and caspase-7. These executioner caspases dismantle the cell by cleaving various cellular substrates, leading to the characteristic morphological changes of apoptosis.

6. **Apoptosis Execution:** The executioner caspases dismantle the cell by cleaving various cellular substrates, leading to the characteristic morphological changes of apoptosis. These changes include nuclear fragmentation, DNA cleavage, cell shrinkage, and the formation of apoptotic bodies.

The apoptosome assembly serves as a crucial control point for the intrinsic apoptotic pathway. Its formation ensures that caspase-9 activation and the apoptotic cascade are triggered only in response to appropriate apoptotic stimuli. Disruption of apoptosome assembly can lead to uncontrolled cell survival and contribute to cancer development.'
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Proteins (1)

Compounds (8)