Apoptosis is the programmed cell death, which occurs in the life cycle of all multicellular organisms.
- It is genetically determined process.
- Apoptosis regulating genes have been found in every organism.
- It occurs during normal cell turnover, development and in the immune system.
- It is an active process that requires energy in the form of ATP.
- It may occur when a cell has become mutated and is on the verge of becoming cancer.
Chief features of apoptosis are as follows:
- Cell shrinkage
- Chromatin condensation
- Preservation of organelles and cell membrane
- Rapid engulfment by neighboring cells prevent inflammation
- The term ‘apoptosis’ was used by Kerr et al. (1972)
- Apoptosis differs from necrosis in which cellular debris can damage the organism.
- Apoptosis involves only single scattered cells.
- In general, apoptosis is advantageous in the life cycle of an organism. For example, differentiation of fingers and toes in a developing embryo occurs because the fingers apoptose, resulting in separation of the digits.
- Excessive apoptosis may cause atrophy, such as in neurodegenerative diseases, while too less apoptosis results in uncontrolled cell proliferation in cancer.
- Apoptosis is highly related with caspases, Bcl-2 proteins and granzyme B.
Apoptosis Triggered by Mitochondrial (Internal Signals) Pathway
- Bcl-2 Protein is present on the outer surface of the mitochondria of a healthy cell that prevents apoptosis.
- Internal damage to the cell results in the migration of the Bax protein to the surface of the mitochondrion.
- Here it inhibits the protective effect of Bcl-2 and it also inserts itself in the outer membrane resulting in the formation of a hole causing release of cytochrome c.
- This cytochrome ‘c’ binds with the protein Apaf-1 (apoptotic protease activating factor-I) resulting in the formation of apoptosomes.
- This apoptosomes binds with caspase-9 and activates it.
- Caspase-9 is cleaved and doing so it activates caspases 3 and 7.
- The activation of these caspases results in the digestion of structural proteins in the cytoplasm as well as degradation of chromosomalDNAand lastly phagocytosis of the cell.
Apoptosis Triggered by External Signals
- Fas and TNF receptors are integral membrane proteins.
- Their receptors domains are exposed to the cell surface.
- Binding of FasL and TNF results in the transmission of a signal to the cytoplasm that activates caspases.
- Caspase-8 activates cascade of caspase activation resulting in phagocytosis of the cell.
Apoptosis-Inducing Factor (ANF)
- Apoptosis-inducing factor is a protein which is generally found in the membrane space of the mitochondria.
- When the cell receives a signal relating to death, the apoptosis-inducing factor is released from the mitochondria.
- It then reaches to nucleus and binds with theDNA.
- Binding results in the fragmentation of theDNAand ultimately death of the cell.
Apoptosis and Diseases
Apoptosis is genetically regulated.
There exists a balance between cell death and cell proliferation and any imbalance between these two results in abnormal expression of genes resulting in disease states.
- Several diseases states have been associated with an abnormal expression of genes involved in programmed cell death such as neurodegenerative diseases (Parkinson’s disease, Huntington’s disease and Alzheimer’s disease) in which there is an increase in apoptosis.
- About half of the known cancers have mutations in one of the key regulators of apoptotic pathway.
- It has been suggested that an increase in apoptosis results in excessive depletion of CD4 cells in patients suffering from Aids.
- Recent researches have revealed that HIV-infected lymphocytes express elevated levels of Fas/Apo-1 receptors on their surfaces.