Programmed cell death
Programmed cell-death (or PCD) is death of a cell in any form, mediated by an intracellular program. PCD is carried out in a regulated process, which usually confers advantage during an organism's life-cycle. For example, the differentiation of fingers and toes in a developing human embryo occurs because cells between the fingers apoptose, or die; the result is that the digits are separate. PCD serves fundamental functions during both plant and metazoa (multicellular animal) tissue development. Apoptosis and autophagy are both forms of PCD, but necrosis is a non-physiological process that occurs as a result of infection or injury.
Apoptosis
Apoptosis is the process of PCD that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation. There appears to be some variation in the morphology and indeed the biochemistry of these "suicide" pathways. Some tread the path of apoptosis, while others follow a more generalized pathway to deletion; however both are usually genetically and synthetically motivated. There is some evidence that certain symptoms of apoptosis, such as endonuclease activation, can be spuriously induced without engaging a genetic cascade; however, it is presumed that true apoptosis and PCD must be genetically mediated. It is also becoming clear that mitosis (the division of the cell nucleus) and apoptosis are linked in some way, and that the balance achieved depends on signals received from appropriate growth or survival factors.
When a cell is damaged, superfluous, or potentially dangerous to an organism, a cell can initiate a mechanism to trigger apoptosis. Apoptosis allows a cell to die in a controlled manner that prevents the release of potentially damaging molecules from inside the cell . There are many internal checkpoints that monitor a cell's health; if abnormalities are observed, a cell can spontaneously initiate the process of apoptosis. However, in some cases, such as a viral infection or uncontrolled cell division due to cancer, the cell's normal checks and balances fail.
Apoptosis can also be initiated via external signaling. For example, most normal animal cells have receptors that interact with the extracellular matrix, a network of glycoproteins that provides structural support for cells in an organism. The binding of cellular receptors to the extracellular matrix initiates a signaling cascade within the cell. However, if the cell moves away from the extracellular matrix, the signaling ceases, and the cell undergoes apoptosis. This system keeps cells from traveling through the body and proliferating out of control, as happens with tumor cells that metastasize.
Another example of external signaling that leads to apoptosis occurs in T-cell development. T-cells are immune cells that bind to foreign macromolecules and particles, and target them for destruction by the immune system. Normally, T-cells do not target "self" proteins (those of their own organism), a process that can lead to autoimmune diseases. In order to develop the ability to discriminate between self and non-self, immature T-cells undergo screening to determine whether they bind to so-called self proteins. If the T-cell receptor binds to self proteins, the cell initiates apoptosis to remove the potentially dangerous cell.
Apoptosis is also essential for normal embryological development. In vertebrates, for example, early stages of development include the formation of web-like tissue between individual fingers and toes . During the course of normal development, these unneeded cells must be eliminated, enabling fully separated fingers and toes to form. A cell signaling mechanism triggers apoptosis, which destroys the cells between the developing digits.
Programmed Cell Death
This histological section of a foot of a 15-day-old mouse embryo, visualized using light microscopy, reveals areas of tissue between the toes, which apoptosis will eliminate before the mouse reaches its full gestational age at 27 days.
Autophagy
Macroautophagy, often referred to as autophagy, is a type of programmed cell death accomplished through self-digestion. It is a catabolic process that results in the autophagosomic-lysosomal degradation of bulk cytoplasmic contents, abnormal protein aggregates, and excess or damaged organelles. Autophagy is generally activated by conditions of nutrient deprivation but has also been associated with physiological as well as pathological processes such as development, differentiation, neurodegenerative diseases, stress (physiology), infection and cancer.
Necrosis
Necrosis is the death of a cell caused by external factors such as trauma or infection and occurs in several different forms. Recently a form of programmed necrosis, called necroptosis, has been recognized as an alternate form of PCD. It is hypothesized that necroptosis can serve as a cell-death backup to apoptosis when the apoptosis signaling is blocked by endogenous or exogenous factors, such as viruses or mutations.