regulation of programmed cell death

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of programmed cell death, cell death resulting from activation of endogenous cellular processes. [GOC:jl]

Programmed cell death, also known as apoptosis, is a tightly regulated process essential for maintaining tissue homeostasis, development, and immunity. It involves a series of biochemical events that lead to the dismantling of the cell without causing damage to neighboring cells.

The process is initiated by various stimuli, including intrinsic (internal) and extrinsic (external) signals.

Intrinsic pathways are triggered by cellular stress, such as DNA damage, hypoxia, or nutrient deprivation. These signals activate the mitochondrial pathway, where proteins like Bax and Bak form pores in the mitochondrial membrane, releasing cytochrome c into the cytosol. Cytochrome c then binds to Apaf-1, forming the apoptosome complex. This complex activates caspase-9, a key executioner caspase, which initiates a cascade of caspase activation.

Extrinsic pathways are triggered by death receptors, such as TNF receptor 1 (TNFR1) and Fas. These receptors bind to their ligands, such as TNF-α and Fas ligand, respectively, triggering the recruitment of adaptor proteins like TRADD and FADD. This complex activates caspase-8, another executioner caspase, which can directly activate downstream caspases or indirectly through the mitochondrial pathway.

The activation of executioner caspases, including caspase-3, -6, and -7, leads to the dismantling of the cell. These caspases cleave various cellular proteins, including lamins (which break down the nuclear envelope), cytoskeletal proteins (which dismantle the cell structure), and DNA repair enzymes (which contribute to DNA fragmentation).

The dying cell exhibits characteristic morphological changes, including cell shrinkage, nuclear fragmentation, and formation of apoptotic bodies. These apoptotic bodies are engulfed by neighboring cells or macrophages, preventing inflammation and maintaining tissue integrity.

Regulation of programmed cell death is critical for maintaining cellular homeostasis and preventing uncontrolled cell proliferation, which can lead to cancer. Dysregulation of apoptosis can also contribute to various diseases, including neurodegenerative disorders, autoimmune diseases, and inflammatory diseases.

The intricate interplay of signaling pathways and effector proteins ensures that programmed cell death occurs in a controlled and specific manner, contributing to the overall health and well-being of the organism.'
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Proteins (3)

Compounds (20)