intrinsic apoptotic signaling pathway in response to osmotic stress

Definition

Target type: biologicalprocess

The series of molecular signals in which an intracellular signal is conveyed to trigger the apoptotic death of a cell. The pathway is induced in response to changes in intracellular ion homeostasis, and ends when the execution phase of apoptosis is triggered. [GOC:mtg_apoptosis, PMID:11454444, PMID:16483738]

Osmotic stress, a condition where cells experience a change in extracellular fluid tonicity, can trigger intrinsic apoptotic signaling pathway. This pathway, also known as the mitochondrial pathway, is a tightly regulated process that ultimately leads to programmed cell death.

Here's a detailed description of the intrinsic apoptotic signaling pathway in response to osmotic stress:

1. **Sensing of osmotic stress:** Cells possess various mechanisms to detect osmotic imbalances. Key players include mechanosensitive ion channels, which respond to changes in membrane tension, and osmotic stress-responsive kinases like MAPKs (mitogen-activated protein kinases).

2. **Disruption of cellular homeostasis:** Osmotic stress can lead to cellular swelling or shrinking, disrupting the delicate balance of intracellular electrolytes and water. This can compromise organelle function, including the mitochondria.

3. **Mitochondrial dysfunction:** Mitochondria are particularly vulnerable to osmotic stress. The influx or efflux of water can disrupt mitochondrial membrane potential, leading to increased permeability and release of pro-apoptotic proteins.

4. **Activation of the Bcl-2 family:** Osmotic stress triggers the activation of pro-apoptotic members of the Bcl-2 family, such as Bax and Bak. These proteins oligomerize and form pores in the mitochondrial outer membrane, leading to the release of cytochrome c.

5. **Caspase activation:** Cytochrome c, once released into the cytosol, binds to apoptotic protease-activating factor-1 (Apaf-1). This complex recruits and activates caspase-9, an initiator caspase. Caspase-9, in turn, activates downstream executioner caspases like caspase-3 and -7.

6. **Execution of apoptosis:** Caspases are proteases that cleave specific substrates, leading to a cascade of events that dismantle the cell. These events include:
- DNA fragmentation: Caspases cleave DNA-repair enzymes and activate endonucleases, leading to DNA fragmentation.
- Cytoskeletal disruption: Caspases cleave cytoskeletal proteins, causing cell shrinkage and membrane blebbing.
- Apoptotic bodies formation: The cell fragments into membrane-bound apoptotic bodies, which are engulfed by neighboring cells or phagocytes.

7. **Removal of apoptotic cells:** Apoptotic cells display "eat me" signals on their surface, attracting phagocytes to engulf and clear them, preventing inflammation.

In summary, osmotic stress triggers a complex cascade of events within the intrinsic apoptotic pathway, ultimately leading to the programmed demise of the cell. This process is tightly regulated to ensure the orderly removal of damaged or dysfunctional cells without causing widespread inflammation.
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Compounds (58)