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  • Writer's pictureDr Edin Hamzić

Shortly About Apoptosis

Apoptosis is cell death that occurs when cells are damaged or no longer needed. It is a natural and essential process that helps to maintain the health and proper functioning of the body. Apoptosis occurs in many scenarios, such as during development when the body grows and changes or in response to infections or other types of damage. As already mentioned, apoptosis is essential for many biological processes, including development, tissue repair, and immune function, and it helps to keep the body healthy by removing cells that could cause harm. Conversely, dysregulation of apoptosis can lead to diseases such as cancer and autoimmune disorders.

What Happens With Cells During Apoptosis?

The other name for apoptosis is programmed cell death because it is a controlled and orderly process regulated by specific proteins and signaling pathways in the cell. When a cell undergoes apoptosis, it shrinks in size, changes shape, and becomes less active. It then breaks down into small pieces, called apoptotic bodies, which are engulfed and removed by other cells, such as immune cells (macrophages), which helps to prevent the release of harmful substances from the dying cell and the onset of inflammation.

Apoptotic bodies are small, membrane-bound fragments of cells that are produced when a cell undergoes apoptosis. Apoptotic bodies are recognized and engulfed by macrophages. Macrophages are equipped with specialized receptors that recognize and bind to apoptotic bodies. Once bound, the macrophage engulfs the apoptotic body, enclosing it within a special compartment called a phagosome. The phagosome then fuses with lysosomes, which contain enzymes that break down and digest the contents of the apoptotic body. In addition to macrophages, other immune cells, such as dendritic cells and eosinophils, may also be involved in removing apoptotic bodies. These cells can also recognize and engulf apoptotic bodies, although their primary role is usually different.

What Types of Apoptosis Are There?

For a long time, instances of cell death have been characterized as apoptotic mainly based on morphologic changes, such as cytoplasmic and nuclear shrinkage (pyknosis), nuclear breakdown (karyorrhexis), and plasma membrane blebbing. However, in the meantime, this morphologic characterization of apoptosis has been abandoned and replaced with a biochemical one.

The biochemical characterization of apoptosis is based on the fact that an instance of regulated cell death is precipitated by the activation of caspase 3 (CASP3). This implies that can be delayed by chemical CASP3 inhibitors as well as by specific genetic interventions that inactivate CASP3.

Apoptosis can be triggered by the activation of either of two distinct but not mutually exclusive signaling pathways that are described as extrinsic and intrinsic apoptosis. Extrinsic apoptosis is initiated by an extracellular stimulus acting on plasma membrane receptors, intrinsic apoptosis follows the permeabilization of mitochondrial membranes driven by an intracellular stimulus.

What Is Intrinsic Apoptosis?

Intrinsic apoptosis, also known as mitochondrial-mediated apoptosis, is a type of programmed cell death that occurs when cells receive signals to die due to internal factors, such as DNA damage or metabolic stress. This process is initiated when proteins called Bcl-2 family members, located on the outer membrane of mitochondria, are activated.

There are two main types of Bcl-2 family members: pro-apoptotic and anti-apoptotic. The pro-apoptotic proteins, such as Bax and Bak, promote the release of cytochrome c from the mitochondria, while the anti-apoptotic proteins, such as Bcl-2 and Bcl-xL, inhibit this process.

When a cell receives a signal to undergo intrinsic apoptosis, the balance between pro-apoptotic and anti-apoptotic proteins is disrupted, leading to the activation of the pro-apoptotic proteins. This leads to the release of cytochrome c from the mitochondria, which activates a group of proteases called caspases, which trigger the cell death process.

Intrinsic apoptosis can be activated by various stimuli, including DNA damage, oxidative stress, and metabolic stress. It is a necessary process that helps to maintain the integrity of tissues and organs by eliminating damaged or unnecessary cells.

What Is Extrinsic Apoptosis?

Extrinsic apoptosis, also known as death receptor-mediated apoptosis, is a type of programmed cell death that occurs when cells receive signals to die due to external factors, such as the presence of specific cytokines or signaling molecules.

This process is initiated when proteins called death receptors, which are located on the surface of cells, are activated by their corresponding ligands. The most well-known death receptors are members of the tumor necrosis factor (TNF) receptor family, including TNFR1 and TNFR2.

When a cell receives a signal to undergo extrinsic apoptosis, the death receptors bind to their ligands and undergo a conformational change that exposes a specific domain called the death domain. This domain recruits and activates a group of proteins called adaptor proteins, activating a group of proteases called caspases, which trigger the cell death process.

Extrinsic apoptosis can be activated by a variety of stimuli, including the presence of specific cytokines, such as TNF-alpha and FasL, and signaling molecules, such as TGF-beta. It is a necessary process that helps to maintain the immune system by eliminating infected or damaged cells.

What Is the Difference Between Extrinsic Apoptosis and Intrinsic Apoptosis?

The main difference between extrinsic and intrinsic apoptosis is the source of the signals that initiate the cell death process, described in the explanations I wrote above.

Intrinsic apoptosis is programmed cell death when cells receive signals to die due to internal factors. This process is initiated by proteins called Bcl-2 family members, located on the outer membrane of mitochondria, and is triggered by the release of cytochrome C from the mitochondria. On the other side, extrinsic apoptosis occurs when cells receive signals to die due to external factors, such as the presence of specific cytokines or signaling molecules. This process is initiated by proteins called death receptors, which are located on the surface of cells, and is triggered by the activation of adaptor proteins and caspases.

In summary, intrinsic apoptosis is initiated by signals from within the cell, while extrinsic apoptosis is initiated by signals from outside the cell. Both processes are essential for maintaining the integrity of tissues and organs by eliminating damaged or unnecessary cells.

What Proteins and Signaling Pathways Are Involved in Apoptosis?

Apoptosis is a complex process regulated by multiple proteins and signaling pathways. Some of the essential proteins and signaling pathways involved in apoptosis include:

  1. Cytosolic proteins. Several cytosolic proteins are involved in the initiation and execution of apoptosis, such as caspases, a family of proteases that cleave and degrade specific substrates, and apoptotic proteases activating factor-1 (Apaf-1), which is a critical component of the apoptosome.

  2. Death receptors. Death receptors are transmembrane proteins that belong to the tumor necrosis factor (TNF) receptor superfamily. They bind to specific ligands and initiate apoptosis by activating intracellular signaling pathways. Examples of death receptors include Fas (also known as CD95), TNF receptor 1 (TNFR1), and TNF-related apoptosis-inducing ligand (TRAIL) receptor 1 (TRAILR1).

  3. Mitochondrial proteins. The mitochondria play a central role in the regulation of apoptosis. Mitochondrial proteins such as cytochrome c, Bcl-2 family proteins, and AIF (apoptosis-inducing factor) are involved in the release of proapoptotic factors and the activation of caspases.

  4. Signal transduction pathways. Several signaling pathways are involved in the regulation of apoptosis. These include the extrinsic pathway, which is activated by death receptors and involves the activation of caspase-8, and the intrinsic pathway, which is activated by mitochondria and activates caspase-9. Both of these pathways ultimately lead to the activation of executioner caspases, which cleave and degrade specific substrates, leading to the execution of apoptosis.


The specific proteins and signaling pathways involved in apoptosis may vary depending on the specific circumstances and the type of cell being targeted.

What Are the Critical Steps of Apoptosis?

The critical steps of apoptosis, or programmed cell death, are:

  1. The cell receives a signal to undergo apoptosis, either from within or outside the cell. This signal is typically triggered by factors such as DNA damage, infection, or hormonal changes.

  2. The cell activates specific proteins, called caspases, responsible for the process of apoptosis.

  3. The caspases cleave or break down other proteins in the cell, including structural proteins, enzymes, and transcription factors. This leads to the breakdown of the cell's organelles, such as mitochondria and the endoplasmic reticulum, and the fragmentation of the cell's DNA.

  4. The cell shrinks in size and becomes less active. Its surface becomes blebbed or covered with small protrusions.

  5. The cell breaks down into small pieces, called apoptotic bodies, which are engulfed and removed by other cells, such as immune cells. This helps to prevent the release of harmful substances from the dying cell and to prevent inflammation.

  6. The cell's remains are cleared away, and the surrounding tissue is repaired.

Overall, apoptosis is a controlled and orderly process essential for maintaining the health and proper functioning of the body. Dysregulation of apoptosis can lead to diseases such as cancer and autoimmune disorders.

What Are Three Examples of Apoptosis?

Three examples of apoptosis, or programmed cell death, are:

  1. During development, apoptosis helps to shape the body by removing cells that are no longer needed or that are in the wrong place. For example, during the formation of the fingers and toes in a developing fetus, apoptosis is used to remove the cells that form the webbing between the digits.

  2. After an infection, apoptosis helps to remove infected cells and to prevent the spread of the infection. For example, when a virus enters a cell, the cell may undergo apoptosis to prevent the virus from replicating and spreading to other cells.

  3. In response to damage or injury, apoptosis helps to remove damaged or unnecessary cells and to promote tissue repair. For example, after a heart attack, apoptosis is used to remove damaged heart tissue and to stimulate the growth of new blood vessels and heart muscle cells.

Overall, apoptosis is a necessary process that helps to maintain the health and proper functioning of the body. Dysregulation of apoptosis can lead to diseases such as cancer and autoimmune disorders.


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