Apoptosis: Cell Suicide

Dec 27, 2011
Michelle Parker

Apoptosis: Programmed Cell Death - Emma Farmer (Own work) [Public domain], via Wikimedia Commons

Apoptosis is a pathway of programmed cell death. It can occur in a either a normal physiological state or a pathologic state.

The word ‘apoptosis’ comes from a Greek word implying “leaves falling from a tree”, most likely referring to the fragmenting of a cell that undergoes apoptosis.

Apoptosis is said be a ‘programmed’ mode of cell death because it is genetically controlled. That is, cells have an innate self-destruction mechanism to actively kill themselves, when the need arises. It is for this reason that apoptosis is described to be suicidal.

Why Does Apoptosis Occur?

Apoptosis, the process of controlled cell death, is necessary for the function of all multicellular organisms, including humans.

Apoptosis occurs under normal physiological conditions, to remove cells that are no longer useful or to maintain cell tissue homeostasis. It plays an important part in the development of the embryo. For example, apoptosis occurs to get rid of cells between the fingers and toes of the embryo to give rise to digits. Apoptosis is required for the rapid turnover of cells of the skin, bone marrow, and gut. In fact, apoptosis is responsible for eliminating 10 billion cells from the body each day, which is quite a huge figure.

Other examples of apoptosis include the shedding of the uterus lining during menstruation, and the removal of white blood cells after an inflammatory or immune response.

Apoptosis is also needed to eliminate cells that have incurred DNA damage that cannot be repaired, and in this way, protects cells from developing mutations and becoming malignant. It is also involved in the purging of infected cells that arise from some infections those caused by a virus.

How a Cell Dies during Apoptosis

In response to signals to undergo apoptosis, a cell activates certain enzymes called caspases, which come from a family of proteases.
These enzymes act by cleaving the cell’s nucleus, proteins and cellular contents. The cell’s nuclear chromatin (DNA and protein) condenses.
The cell shrinks and breaks up into membrane-bound apoptotic fragments
The apoptotic cell fragments are then engulfed and destroyed by neighbouring cells or macrophages (white blood cells), and no adverse reaction occurs (i.e. inflammation)

How Apoptosis Occurs

There are two pathways by which apoptosis can take place. They are the mitochondrial pathway and the death receptor pathway. Each pathway activates initiator caspases which trigger a cascade of caspases and ultimately, apoptosis.

Mitochondrial Pathway

The mitochondrial pathway is the so-called ‘intrinsic’ pathway of apoptosis because it comes from within the cell. This pathway is activated following cellular stress; mainly by DNA damage and by withdrawal of survival signals, such as growth factors and hormones, in a cell.

The mitochondria of cells contain proteins, like cytochrome C, that are pro-apoptotic because they are capable of activating caspases that cause apoptosis. Another group of proteins in the mitochondria, members of the Bcl-2 family, control whether or not these pro-apoptotic proteins are released from the mitochondria and into the cytosol. When a cell encounters some form of cellular stress, Bcl-2 family activates proteins that enable the leakage of pro-apoptotic proteins, including cytochrome C, into the cytoplasm. This leads to the activation of the caspase cascade, which in turn triggers apoptosis.

Death-Receptor Pathway

The other pathway, the death receptor pathway relies on the stimulation of death receptors by external signals. Most cells have ‘death receptors’ on their surfaces. These cells tend to be members of the Tumour Necrosis Factor (TNF) receptor family. When members of the TNF family bind to the death receptors of the TNF receptor family, a death-inducing signalling complex is formed, which in turn activates the caspase cascade. For example, T cell lymphocytes, which are a type of white blood cell of the immune system, express Fas-ligand, a member of the TNF family. When T cells identify and bind to a cell expressing Fas (a death receptor) on their surface, caspases are activated and apoptosis is triggered.

It is possible that the caspases activated via the death receptor pathway, can activate a pro-apoptotic member of the Bcl-2 family, resulting in the activation of the mitochondrial pathway of apoptosis as well.

Apoptosis – A Tightly Regulated Process

It can be seen that apoptosis is indeed a process that is highly regulated. Whether or not a cell undergoes apoptosis depends on intracellular or extracellular signals, which is mediated by the mitochondrial pathway or the death receptor pathway.

References

Hotchkiss, R.S., Strasser, A., McDunn, J.E., & Swanson, P.E. (2009). Cell Death. The New England Journal of Medicine. 361:1570-83.
Duprez, L., Wirawan, E., Berghe, T.V., & Vandenabeele, P. (2009). Major cell death pathways at a glance. Microbes and Infection 11. 1050-1062.
Kumar, V., Abbas, A. K., Fausto, N., & Aster, J. C. (2008). Robbins Basic Pathology. (8th ed.). Philadelphia: Saunders Elsevier.