regulation of programmed necrotic cell death

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of programmed necrotic cell death. [GOC:aruk, GOC:rph, PMID:27258785]

Programmed necrotic cell death, also known as necroptosis, is a regulated form of cell death that shares similarities with both apoptosis and necrosis. While apoptosis is a highly controlled process that results in the orderly dismantling of the cell, necrosis is often considered an uncontrolled, chaotic process caused by external factors such as toxins or injury. Necroptosis, however, is a genetically regulated process that can be initiated by various stimuli, including TNFα, TRAIL, and bacterial toxins. Unlike apoptosis, which relies on caspases, necroptosis is caspase-independent and relies on a specific pathway involving receptor interacting protein kinases (RIPKs) and mixed lineage kinase domain-like protein (MLKL).

The process typically begins with the activation of a death receptor, such as TNFα receptor 1 (TNFR1), which recruits adaptor proteins like TRADD and RIP1 to form a complex. This complex then activates RIP3, which subsequently phosphorylates MLKL. Phosphorylated MLKL translocates to the cell membrane where it oligomerizes and disrupts the membrane integrity, ultimately leading to the cell's demise.

Necroptosis differs from apoptosis in several key ways. Firstly, it is caspase-independent, meaning that it does not rely on the activation of caspases, a family of proteases involved in apoptotic pathways. Secondly, necroptosis is characterized by the release of cellular contents into the extracellular space, which can trigger inflammation and other cellular responses. Thirdly, unlike apoptosis, which is often triggered by internal stimuli, necroptosis is typically induced by external factors like pathogens, toxins, or stress.

Necroptosis plays a significant role in various biological processes, including development, immunity, and inflammation. In development, necroptosis helps shape tissues and organs by removing unwanted cells. In immunity, necroptosis plays a role in defense against pathogens by killing infected cells and triggering an inflammatory response. However, dysregulation of necroptosis can contribute to various diseases, including neurodegenerative diseases, inflammatory disorders, and cancer.

In summary, necroptosis is a regulated form of cell death that is distinct from both apoptosis and necrosis. It relies on a specific pathway involving RIPKs and MLKL and plays a crucial role in various biological processes, both in health and disease. It is an area of active research, and a deeper understanding of necroptosis could pave the way for novel therapeutic interventions for a range of diseases.'
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Proteins (1)

Compounds (3)