Overview

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue. After examining the tissue under an electron microscope, he observed that the hepatocytes had shrunk and the chromatin had condensed. In 1980, Wyllie established the relationship between DNA degradation and apoptosis.

Apoptosis allows a cell to die in a controlled manner that prevents the release of potentially damaging molecules from inside the cell to the extracellular space. Many internal checkpoints monitor a cell's health. If abnormalities are observed, a cell can spontaneously initiate apoptosis. However, the cell's standard checks and balances fail in some cases, such as during viral infection or uncontrolled cell division due to cancer. External signaling can also initiate apoptosis. For example, most normal animal cells have receptors that interact with the extracellular matrix, a network of glycoproteins that provides structural support for cells in an organism. The binding of cellular receptors to the extracellular matrix initiates a signaling cascade within the cell. However, if the cell moves away from the extracellular matrix, the signaling ceases, and the cell undergoes apoptosis. This system prevents cells from traveling through the body and proliferating out of control, as happens with tumor cells that metastasize.

Regulated apoptosis is essential to maintain normal physiology and tissue homeostasis. Dysregulated apoptosis in cells leads to various diseases, such as cancer, Alzheimer's, and cardiovascular diseases. Dysregulated apoptosis can also cause increased apoptosis, as observed during various autoimmune diseases like Hashimoto's thyroiditis, systemic lupus erythematosus, and rheumatoid arthritis.

Some portion of this text is adapted from Openstax, Biology 2e, Section: 9.3

Procedure

Apoptosis is a programmed cell death process where specific signals lead to the death of unwanted or potentially harmful cells.

The intrinsic or mitochondrial-mediated apoptotic pathway is triggered by intracellular death signals produced due to DNA damage, hypoxia, and biochemical stress such as oxidative stress. In contrast, the extrinsic apoptotic pathway is initiated when extracellular death-inducing ligands, such as cytokines, bind to the death receptors present on the cell surface.

The key mediators of apoptosis are proteases called caspases. Initiator caspases are activated by both intrinsic and extrinsic apoptotic pathways through different mechanisms.

Each initiator caspase then activates multiple executioner caspases.

In both pathways, the activated executioner caspases cleave cellular proteins causing morphological changes, such as cell shrinkage, nuclear fragmentation, and plasma membrane blebbing.

Next, the cellular components are enclosed into membrane vesicles called apoptotic bodies, which are then engulfed by phagocytic cells.

Through these steps, apoptosis results in controlled and contained cell death without causing inflammation and damage to the neighboring cells.