Apoptosis is the process of programmed cell death. It is one of the wonders of biology. Another miracle that mother Nature has in store for us. To me, after Mitosis, this is the second most marvelous miracle of the human life.
From its early conceptual beginnings in the 1950s, it has exploded as an area of research within the life sciences community. As well as its implication in many diseases, it is an integral part of biological development. It is mostly associated with cancer and cancer research. If a cell does not stop dividing when it is injured, it will continue to divide endlessly and a tumor will be formed. Cancer will ensue.
That’s right, you understood well: A cell may receive an order to die! To commit suicide. How is this possible you might wonder?
This, of course, is a necessity based on survival “instincts” of a multicellular body. In fact, the regulation of how cell dies is a very controlled process. The marvelous thing is that such program is actually permanently activated in cell, it is always ready to act. Always protecting the cell and the body as a whole. The only way for a cell to continue living is in performing certain normal job, which it is supposed to keep performing. Then the action of apoptosis is being delayed up until the cell is performing something else, something unnatural. Then it kicks in. Once started, apoptosis cannot be stopped.
Where does the word come from?
In an article published in 1972, John F. Kerr, Andrew H. Wyllie and A. R. Currie, coined the term “apoptosis” in order to differentiate naturally occurring developmental cell death from the necrosis that results from acute tissue injury. They adopted the Greek word for the process of leaves falling from trees or petals falling from flowers. The word apoptosis is a combination of the prefix ‘apo‘ and the root ‘ptosis‘. Apo means away, off or apart. Ptosis means to fall. So then, the closest translation of apoptosis is “to fall apart”.
The 2002 Nobel Prize in Medicine was awarded to Sydney Brenner, H. Robert Horvitz and John E. Sulston for their work identifying genes that control apoptosis.
How does it work?
Apoptosis is a complex process and it is a constant source of biology and cancer research.
In multicellular organisms, the total number of cells is a balance between the cell-generating effects of mitosis (cellular division) and cell death that is induced through apoptosis. A disruption of this delicate balance can lead to the development of cancer.
I will try to explain its mechanisms in simple terms so you can have a good grasp of what is going on.
A neuron that undergoes apoptosis
The cell is the unit of life. The call has receptors on its surface. The cell is supposed to perform functions that have been encoded in its genetic base. A liver cell will always perform liver functions, for example.
The receptors direct the constant flow of information from outside the cell to nucleus. The cell is always in contact with its environment through chemical means. There is always information that comes from inside of the cell to the nucleus and from outside the cell to the nucleus. An intrinsic pathway and an extrinsic pathway, in more scientific terms.
There is certain genes (the “night guards”) that passively “observe” this flow of information.
If there is something wrong with the cell, these genes immediately stop all normal activity of the cell and let it repair itself and return to normality. They will always give it a chance to live first. If this does not happen in a timely manner, these genes activates other family of genes (which I will call “jury” as it plays this role), all together 16 such genes, 10 of them are always pro-apoptosis (let’s associate them with the +” sign), and 6 are against apoptosis (I will associate them with the “-” sign). This jury computes the signals coming from inside and outside of the call and ultimately makes a decision. Ultimately, this decides the fate of the cell.
- If there are many “+” signals that overwhelm the “–” signals, the genes order the cell to commit suicide. The cell will rapidly die. It is in the best interest of the body. It is the ultimate altruism. Sacrifice for the greater good. “You need to die”, it tells the cell. “You cannot continue like this. We will find a suitable (and healthy, normal) replacement for you so that all of us can survive”.
- If there are more “–” signals that overwhelm the “+” signals, the cell will live. Everything will go back to normal. The cell will repair itself. The damage is not too great and can be fixed. The Night guards will keep monitoring the cell, inside and out. Always on guard for the greater good.
What constitute a “+” signal? When does the apoptosis start?
Such signals can come when there is an infection with bacteria or a virus. Also, when the cell is normal but no longer needed, such as cells that produce antibodies after the need for the antibody has passed. That will generate strong “+” signals. Apoptosis can also be triggered in otherwise normal cells by external stimuli, including nutrient removal, toxins, hormones, heat, and radiation. Also low oxygen concentration or high calcium concentration in the cell. It is estimated that a mass of cells equal to body weight is removed by apoptosis each year. In this case, the genes will issue “+” signals to the cell to start apoptosis, because they need to protect the body as a whole.
What happens with the dead cell?
Apoptosis progresses quickly and its products are quickly removed, making it difficult to detect or visualize this process. Tests for DNA laddering differentiate apoptosis from ischemic or toxic cell death.
The removal of dead cells by neighboring phagocytic cells has been termed efferocytosis. Dying cells that undergo the final stages of apoptosis display phagocytotic molecules, on their cell surface. These molecules mark the cell for phagocytosis by cells possessing the appropriate receptors, such as macrophages. The removal of dying cells by phagocytes occurs in an orderly manner without eliciting an inflammatory response. Everything is efficient and neat. Nature at its best.