positive regulation of intrinsic apoptotic signaling pathway in response to osmotic stress

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of intrinsic apoptotic signaling pathway in response to osmotic stress. [GOC:BHF, GOC:mtg_apoptosis, GOC:rl, GOC:TermGenie, PMID:14569084]

Osmotic stress, a condition where cells experience changes in their extracellular solute concentration, triggers a complex cellular response involving the activation of the intrinsic apoptotic pathway. This pathway is a key mechanism for eliminating damaged or unwanted cells, and its activation under osmotic stress ensures the removal of cells that are unable to adapt to the altered environment.

The process begins with the disruption of cellular homeostasis caused by osmotic stress. This disruption can lead to an increase in intracellular reactive oxygen species (ROS) and the activation of stress-activated protein kinases (SAPKs), such as JNK and p38.

Activation of these kinases can lead to the phosphorylation of pro-apoptotic proteins like Bcl-2 family members. Specifically, pro-apoptotic members like Bax and Bak are activated, leading to the disruption of mitochondrial membrane potential and the release of cytochrome c into the cytosol.

Cytochrome c, together with apoptotic protease activating factor 1 (Apaf-1) and procaspase-9, forms the apoptosome complex. This complex activates caspase-9, an initiator caspase, which in turn activates downstream executioner caspases, such as caspase-3 and caspase-7.

These executioner caspases cleave various cellular substrates, leading to the dismantling of the cell. Key targets include proteins involved in DNA repair, cell cycle regulation, and cytoskeletal organization. This ultimately results in the characteristic apoptotic features like DNA fragmentation, nuclear condensation, and cell shrinkage.

In addition to the core signaling cascade, other pathways contribute to the positive regulation of intrinsic apoptosis in response to osmotic stress. These include the involvement of death receptor signaling pathways, the accumulation of misfolded proteins within the endoplasmic reticulum, and the activation of autophagy.

The overall process is tightly regulated to ensure that apoptosis is only initiated in response to appropriate stimuli and that it is executed efficiently. Disruptions in this delicate balance can lead to various diseases, including cancer, neurodegenerative disorders, and autoimmune diseases.'
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Proteins (1)

Compounds (8)