Cells present in multicellular organisms possess the unique property of self-destruction. They have the genetic information to commit suicide! This phenomenon is termed as programmed cell death (PCD).
Animal cells contain genetic information for a process called apoptosis, which involves destructive proteins that chew off all the cellular contents and package them into vesicles. These vesicles are engulfed by phagocytic or scavenger cells of the body and further degraded to release sugars, amino acids, and nucleotides. These molecules are used as building blocks in the synthesis of new macromolecules and cellular components. No component of the dying cell is wasted, and every molecule is utilized. In case of plants and fungi, PCD has been observed, but the underlying molecular mechanisms are comparatively less understood.
However, what intrigues scientists the most is why do cells commit suicide, and how does the organism benefit by losing its cells. This Buzzle write-up tries to explain the altruism behind cell suicide in animals, and how it is essential for their proper embryonic development as well as healthy survival.
Why Cells Commit Suicide?
For Sculpting the Body
The early developmental stages of organisms are characterized by controlled proliferation and differentiation of cells, as well as the controlled and planned death of certain cells. Certain cells are programmed to die at specific stages of embryonic development. This is essential for sculpting the right shape as well as elimination of certain structures, especially during metamorphosis.
Cell suicide during early developmental stages
» The most well-studied example of deletion of structures through cell suicide is the elimination of tail during the early developmental stages in frogs. Tadpoles do not have arms and legs, but a have tail that enables them to swim around. During metamorphosis in the 9- to 10-week-old tadpoles, thyroid hormone stimulates the suicidal pathways in cells present in the tail. The tail, thus, degenerates, and limb formation occurs simultaneously.
» Another key process where cell suicide is necessary is the formation of digits or fingers in vertebrates. The early structure that develops into hands or feet is a plate-like structure comprising digits fused through interdigital tissues. The cells in this interdigital tissue commit suicide, thus, giving rise to free digits or fingers. In animals with webbed feet, (for example, duck), such elimination of cells in the interdigital region does not occur.
Other animal developmental processes that involve apoptosis are bone development and formation of joints in vertebrates, intestine development in frogs, salivary gland and midgut development in flies, as well as the metamorphosis of several insects, including fruit flies, butterflies, and moths. In addition, unfertilized eggs of organisms that reproduce through external fertilization also exhibit death through apoptosis.
Similar events take place during the development of plant structures. PCD is essential for determining the leaf shape and formation of reproductive structures.
In Response to Abnormality
Cells have distinct mechanisms to ensure that every newly formed component is perfect, and that every function or process is taking place in a normal manner. In addition to this, they also have the ability to initiate repair mechanisms in case any structural defect is detected.
Cell suicide in case of DNA damage
If such repair mechanisms fail with respect to the vital macromolecules, like DNA, the cell does not multiply, but initiates self-destruction. DNA damage may occur due to several factors, like radiation, reactive oxygen species, carcinogens, and erroneous DNA replication.
Molecular checkpoints that operate during the different stages of cell division are essential for such quality control. When a defect like DNA damage is detected, cell division is halted and repair mechanisms are initiated. If the defect is beyond repair, and repair mechanisms fail to rectify the error, PCD is initiated, and the cell commits suicide.
Such cell death ensures that the organism is free of defective cells, and the normal functions of the tissue are not affected.
When They Grow Old
The most mind-boggling phenomenon in cells is the mechanism through which they determine their own age, and when old enough and susceptible to damage, they commit suicide. Every single day, millions of cells die and are replaced by new cells―a process called cell turnover
Cell suicide due to aging
Each cell type has a fixed lifespan, and it commits suicide when this time span is over. One of the ways through which this is achieved is the presence of structures called telomeres that form the protective caps for chromosomes. The length of these telomeres reduces with each cell division, due to the discontinuous DNA replication of the lagging strand. Ultimately, the entire telomere is lost, as a result of which chromosomes break off and/or stick to each other. This genomic instability is detected during cell division, and the suicidal pathways are activated.
In all adult tissues, cell death and cell division are intricately balanced to maintain the optimum size of the tissue. A special case of this is the liver, which is capable of regenerating lost tissue. An experiment on rat liver revealed an interesting fact. When a part of the liver was removed, the cells could sense this, and cell division increased to build the lost part. An opposite scenario was created by artificially inducing cell divisions through a chemical agent, to obtain an enlarged liver. When the administration of the chemical was stopped, cell death occurred at a high rate to reduce the liver size back to normal.
Plants even utilize the process of cell suicide to destroy an entire organ or tissue, that is no longer required. This helps to optimize the utilization of available resources, and limits the sites for pathogen entry. The falling of petals and sepals after pollination is the result of such cell suicide.
When They Are Unfit for a Particular Role
The immune system of animals comprises a set of soldier cells and molecules that defend the body from foreign invaders, like pathogens and pathogenic determinants. Cell suicide through apoptosis is the central process for eliminating the soldier cells that act against the body itself.
Cell suicide in immune cells
The two major types of immune cells present in the body include T cells (T lymphocytes) and B cells (B lymphocytes). Immature T cells are formed in the bone marrow and migrate to the thymus for further differentiation and maturation, whereas the immature B cells complete their development in the bone marrow itself. How do these soldiers know to differentiate foreign matter from self-proteins or organs, you may ask. This is achieved through specific receptors present on their surface which can recognize antigens.
The immature T cells that enter the thymus are tested for the function of their receptors, failing which the suicidal pathway gets activated. If the receptors are correctly functioning, they are tested for self-reactivity, that is, their affinity towards self-antigens is evaluated. The cells that have high affinity for self-antigens (cells which fail the test) are forced to commit suicide.
Similar events occur in the development and maturation of B cells. These cells recognize foreign antigens through membrane-bound antibodies. The immature B cells are subjected to a similar self-reactivity test, failing which the antibodies are edited, and the cells are tested again. The cells that comply proceed to maturation, whereas those which bind to self-antigens undergo apoptosis.
In addition to this, when immune or certain plant cells get infected by pathogens and are unable to intracellularly kill them, they bring about their own demise. This ensures that the pathogen is broken down and destroyed. This is especially observed during viral infections. In plants, such cell death is observed as a part of the hypersensitive response (HR) mechanism that operates in the event of an infection.
The balance between the formation of new cells and deletion of the old and abnormal cells is vital for all physiological processes of the body. Further insights into
, and how it can be induced or prevented can provide clues for the treatment of several diseases.