apoptotic signaling pathway

Definition

Target type: biologicalprocess

The series of molecular signals which triggers the apoptotic death of a cell. The pathway starts with reception of a signal, and ends when the execution phase of apoptosis is triggered. [GOC:mtg_apoptosis]

Apoptosis, also known as programmed cell death, is a highly regulated process that eliminates unwanted or damaged cells in multicellular organisms. It involves a cascade of molecular events that ultimately lead to the dismantling of the cell. The apoptotic signaling pathway is a complex network of signaling molecules, including receptors, adaptor proteins, kinases, and caspases, that orchestrate the process.

**Initiation:**

* **Extrinsic Pathway:** This pathway is triggered by external stimuli, such as death ligands (e.g., TNF-alpha, FasL) binding to their respective death receptors (e.g., TNF receptor 1, Fas). This interaction activates adaptor proteins (e.g., FADD), which recruit and activate caspase-8.
* **Intrinsic Pathway:** This pathway is initiated by internal stressors like DNA damage, oxidative stress, or growth factor deprivation. It involves mitochondria releasing pro-apoptotic factors (e.g., cytochrome c), which bind to Apaf-1, forming the apoptosome complex. This complex activates caspase-9.

**Execution:**

* **Caspase Activation:** Both pathways ultimately converge on the activation of executioner caspases, primarily caspase-3 and -7. These proteases dismantle the cell by cleaving key structural proteins.
* **Cell Dismantle:** Caspase-3 and -7 cleave a variety of proteins, leading to:
* Fragmentation of DNA: Apoptotic enzymes cleave DNA into fragments, resulting in a "ladder-like" pattern when visualized by electrophoresis.
* Breakdown of cytoskeleton: This leads to cell shrinkage and rounding.
* Formation of apoptotic bodies: The cell membrane blebs and fragments into apoptotic bodies containing cell debris, which are phagocytosed by neighboring cells or macrophages.

**Regulation:**

* **Anti-apoptotic proteins:** Apoptotic signaling is tightly regulated by anti-apoptotic proteins, such as Bcl-2 and Bcl-xL, which prevent the release of cytochrome c from mitochondria.
* **Survival factors:** Growth factors and other survival signals can activate anti-apoptotic pathways, preventing apoptosis.

**Significance:**

* **Tissue homeostasis:** Apoptosis is essential for maintaining tissue homeostasis by eliminating cells that are no longer needed or are damaged.
* **Development:** Apoptosis plays crucial roles in development, such as shaping tissues and organs, removing unwanted cells, and sculpting structures.
* **Disease prevention:** Defects in apoptotic pathways can contribute to various diseases, including cancer, autoimmune disorders, and neurodegenerative diseases.

Apoptosis is a highly complex process with multiple pathways and regulatory mechanisms. Understanding the intricate details of this process is crucial for developing therapeutic strategies targeting apoptosis in various diseases.'
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Proteins (27)

Compounds (771)