negative regulation of execution phase of apoptosis

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of execution phase of apoptosis. [GOC:mtg_apoptosis, GOC:TermGenie]

Negative regulation of execution phase of apoptosis refers to the cellular processes that actively prevent or inhibit the final stages of programmed cell death, also known as apoptosis. This intricate regulatory mechanism is crucial for maintaining tissue homeostasis and preventing uncontrolled cell death. Here's a breakdown of the key aspects:

**1. Activation of Apoptosis:**
- Apoptosis is initiated by intrinsic (internal) or extrinsic (external) pathways.
- Intrinsic pathway involves cellular stress, DNA damage, and mitochondrial dysfunction, ultimately leading to the release of cytochrome c from mitochondria.
- Extrinsic pathway involves death receptor activation, such as TNFα, Fas, or TRAIL, triggering caspase cascades.

**2. Execution Phase of Apoptosis:**
- This phase involves the activation of executioner caspases (caspase-3, -6, and -7), which cleave specific target proteins within the cell.
- These cleavages lead to characteristic apoptotic features, such as DNA fragmentation, cell shrinkage, and formation of apoptotic bodies.

**3. Negative Regulation Mechanisms:**
- **Inhibition of Caspase Activation:**
- **Caspase Inhibitors:** Proteins like IAPs (inhibitor of apoptosis proteins) bind to and inhibit activated caspases, preventing their proteolytic activity.
- **Apoptosis-Inducing Factor (AIF):** This protein, released from mitochondria, can interact with IAPs and promote their degradation, thereby indirectly activating caspases.
- **Regulation of Mitochondrial Integrity:**
- **Anti-Apoptotic Bcl-2 Family Members:** Proteins like Bcl-2, Bcl-xL, and Mcl-1 bind to pro-apoptotic Bcl-2 family members (e.g., Bax and Bak) and block their ability to permeabilize the mitochondrial membrane. This prevents the release of cytochrome c and other apoptogenic factors.
- **Mitochondrial Membrane Potential Maintenance:** Processes that ensure mitochondrial integrity, such as ATP production and reactive oxygen species (ROS) scavenging, contribute to preventing mitochondrial membrane permeabilization and subsequent apoptosis.
- **Signal Transduction Pathways:**
- **Survival Signaling:** Activation of pathways involving PI3K/Akt and NF-κB promotes cell survival by inhibiting pro-apoptotic signals and enhancing anti-apoptotic mechanisms.
- **Autophagy:** This cellular process, often triggered by nutrient deprivation or stress, can act as a survival mechanism by degrading damaged components and providing energy. In some cases, autophagy can also contribute to apoptosis.

**4. Importance of Negative Regulation:**
- **Tissue Homeostasis:** Preventing excessive apoptosis is crucial for maintaining tissue integrity and function.
- **Immune System Regulation:** Proper negative regulation of apoptosis is essential for controlling immune responses and preventing autoimmune disorders.
- **Developmental Processes:** Apoptosis plays a role in development, and its regulation ensures proper tissue formation and removal of unwanted cells.
- **Cancer:** Dysregulation of apoptosis pathways can contribute to the development and progression of cancer.

**Note:** Negative regulation of apoptosis is a complex process involving numerous pathways and interacting components. It is tightly controlled to ensure appropriate responses to various cellular stimuli.'
"

Proteins (1)

Compounds (35)