By Mohamed Mahmoud
Have you ever imagined that cells can die by suicide or thought of how and why they would do so? The answer is yes! Cells undergo cellular suicide for the good of the whole system. This cellular suicide process is a tightly controlled process called apoptosis. In Ancient Greek, apoptosis means to “fall off”. Apoptosis is referred to as the process of programmed cell death. In apoptosis, cells undergo a cascade of actions to make sure they do not release their contents to their surroundings. This cascade of actions starts by chromatin condensation, then membrane blebbing followed by nuclear collapse, and finally apoptotic body formation (Figure 1).
The resultant apoptotic bodies can be collected and digested by the immune cells, avoiding an inflammatory immune response. This is one of the differences between apoptosis and necrosis. Necrosis refers to cell death, but not a programmed cell death. In necrosis, cells die by different factors such as injury, chemicals, or harsh environment and release their contents to the surroundings which elicits an inflammatory immune response.
The question now is what activates apoptosis? Apoptosis has 2 main pathways: intrinsic and extrinsic pathways. In the extrinsic pathway, apoptosis is activated upon an outside signal that activates the death receptors on the surface of the cells. In the intrinsic pathway, the signal is internal and it mainly comes from the mitochondria (Figure 2)
As mentioned earlier, in apoptosis, cells die by suicide for the good of other cells and the organism as a whole. How is this possible? In order to answer this, we need to know more about why apoptosis is important. Apoptosis is involved in various vital processes including developmental processes, host defense, and tumor initiation prevention. Apoptosis has been shown to play an important role in early developmental changes. In 2002, The Nobel Prize in Physiology or Medicine was awarded for the discoveries of apoptosis’ role in organ development. During development, apoptosis is involved in unwanted tissue removal and organ sculpting. As shown in Figure 3, an example of the unwanted tissue removal is the tadpole tail removal when changing into a frog. Moreover, figure 3 also shows how apoptosis is responsible for interdigital spaces (spaces between finger and toes) formation. Absence of apoptosis during development can lead to syndactyly, a condition in which digits (fingers or toes) are conjoined.
In addition to development, apoptosis aids in host defense against viruses. Virus-infected cells undergo apoptosis, forming apoptotic bodies. This will limit the spread of viral particles to other cells (Figure 4).
Lastly, one of the most vital aspects in which apoptosis takes part is tumor initiation prevention. After several divisions and over time, cells start to get exhausted and accumulate DNA damage. This DNA damage acts as a signal to initiate apoptosis. If such cells are able to evade apoptosis, they can further divide and accumulate more DNA damage, changing into cancerous cells and forming tumors. Scientists, therefore, consider apoptosis as a promising therapeutic target in cancer cells.
In summary, it’s important to consider that apoptosis should be balanced. Too much apoptosis can lead to deleterious effects where too many cells are dying. This can lead to neurodegenerative diseases including Parkinson’s, Alzheimer’s, and Huntington’s diseases. On the other hand, too little apoptosis can lead to cancer, compromise host defense against viruses, and cause developmental-related morphological abnormalities.
