An Importance of Apoptosis to All Aspects of All Organisms

Apoptosis Pathway

Cell signaling pathways control nearly every aspect of the cell, and therefore of the body. The job of a cell signaling pathway is to convert a signal, such as a hormone, into a response (Signaling Pathway 2007). There are three parts of cell signaling pathways: reception, transduction, and response. Reception is the first stage in cell signaling. This step uses a ligand (a signaling molecule) to bind to the receptor, which is generally in the cell membrane. Transduction is the second phase in cell signaling. This is a pathway that involves different molecules. This pathway converts the signal that was received into a form that can bring about a certain response. Transduction involves a sequence of changes in a series of different molecules called a signal transduction pathway. Response is the third and final step of cell signaling. The response is the final step of the signal transduction pathway that leads to regulation of one or more cellular processes (Urry 2014). Apoptosis is a type of cell signaling pathway that is crucial to the life of all living organisms.

Apoptosis is known as programmed cell death. This is the body’s way of disposing of damaged, unwanted, or unneeded cells. Apoptosis is crucial to everyday cell life and without it, the body would have no way of disposing of cells. There are two different types of apoptosis, extrinsic and intrinsic. The main difference between the two is where the initiator signal comes from to start the pathway of apoptosis (Cooper 2013).

The initiator signal for extrinsic apoptosis comes from outside of the cell. The ligand, a tumor necrosis factor, binds to the death domain receptor protein, which activates DISC – death inducing signaling cascade. Once this is activated, the DISC interacts with procaspase-8, cleaving it and activating it, changing it to caspase-8. Caspase-8 interacts with procaspase-3, cleaving and activating it, changing it to caspase-3 (Elmore 2007).

In intrinsic apoptosis, the pathway begins from inside of the cell because there is damage or stress within the cell, such as DNA damage. There are molecules within the cell that sense the damage, such as C-terminal Src kinase (CHK) (Chong 2005). They activate p53, a very important protein in multicellular organisms, which functions to suppress cancer. P53 is crucial to conserving stability by preventing genome mutation (Bioinformatics). This protein will halt the cell in the cell cycle. It also recruits other proteins such as Bax, which creates holes in the mitochondria, allowing cytochrome C to be released which then interacts with Apaf 1, a cytosolic protein. Together they activate caspase-9 (procaspase-9 originally) and all together form an Apoptosome. The Apoptosome will then interact with caspase-3 (Elmore 2007).

Both pathways, extrinsic and intrinsic, result in the activation of a protein called caspase-3. This is a death protein. Caspase-3 activates a nuclease enzyme by breaking down the inhibitor that is bound to it. The nuclease enzyme activates proteases and nucleases. The proteases break down the proteins within the cell while the nucleases break down nucleic acids. The breaking down of these cellular components leads to the formation of blebs. Blebs are produced when the cell detaches its cytoskeleton from the membrane, causing the membrane to form spherical bubbles. The blebs are then separated and can be engulfed by phagocytic cells (Elmore 2007).

One aspect that may be confusing is the difference between apoptosis and necrosis. Necrosis refers to tissue death, which is uncontrolled, unlike apoptosis. This type of tissue death could be due to a lack of oxygen or some other type of cell stress or injury. Necrosis is degenerative, passive cell death while apoptosis is a gene directed, active form of cell elimination (Haanen 1995). Cells that die via necrosis swell and burst, releasing their contents into the extracellular space, causing inflammation. In contrast, during apoptosis, chromosomal DNA is fragmented, chromatin condenses, the nucleus breaks into small pieces, and the cell shrinks and breaks into membrane-enclosed fragments called blebs and are then phagocytized. The blebs act as small containers to dispose of the contents within.

Another important function of apoptosis is allowing for development in all living organisms. Around 10 billion cells die every day just to keep balance with the numbers of new cells arising (Renehan 2001). The fingers and toes of mammals begin as webbed structures, looking like the feet of a duck; but, the cells die between digit and form individual fingers and toes (Bruce 1983). Apoptosis is used in mammalian nervous system development to eliminate around 50 percent of developing neurons (Cooper 2013). In animals such as chickens, apoptosis is also very important. In chickens, the webbing between their feet undergo BMP-mediated apoptosis while in ducks, the BMP inhibitor is synthesized, causing this cell death to be blocked. This same sort of situation occurs in bats (Gilbert 2010). Because apoptosis is so important, defective apoptosis can lead to developmental abnormalities (Haanen 1995).

Certain viruses have developed strategies to inhibit apoptosis following a viral invasion, prolonging the life of the infected target cells and promoting virus replication (Haanen 1995). Many cancer cells fail to undergo apoptosis and therefore exhibit increased life spans, contributing to tumor development (Cooper 2013). Normal cells undergo apoptosis following DNA damage, while many cancer cells fail to do so. This contributes to the resistance of cancer cells to irradiation and many chemotherapeutic drugs, which act by damaging DNA (Cooper 2013).

Apoptosis is crucial to all aspects of all organisms. Many may find it interesting that cells kill themselves on purpose, but it is an amazing self defense system. One of the most important jobs of apoptosis occurs during development, but there are numerous jobs apoptosis is responsible for.