Apoptosis

In this post we'll take a look at the differences between apoptosis and necrosis, as well as the two different mechanisms of apoptosis. 

Apoptosis is different to necrosis because it is death that is programmed and is associated with shrinkage of the cell. Apoptosis is a normal mechanism in the body and it plays an important role during development and the maintenance of cell turnover. In the maintenance of cell turnover, apoptosis balances mitosis and maintains a constant number of cells in the tissue. During development it works to remove unnecessary tissues such as the webbing between the fingers and forming lumens in tubular organs. Importantly, apoptosis also triggers the death of the cell when there is irreparable damage to the genome and this helps to prevent cancer.

When apoptosis occurs, the cell dies in a way that avoids any inflammatory response by the body and does not create any cellular debris. Once the cell has died, it is cleaned away efficiently by macrophages.

Apoptosis vs Necrosis

Apoptosis often affects single cells while necrosis will affect groups of cells. As mentioned earlier, apoptosis causes the cell to shrink in size while necrosis causes the cell to swell. Necrosis causes nuclear lysis while in apoptosis, the chromatin condenses and the nucleus fragments. In addition, the cell membrane is damaged in necrosis while it remains intact in apoptosis. The cytoplasm of cells that die from apoptosis is packed into apoptotic bodies, in necrosis the cytoplasm is released into the surrounding tissue.

In addition, apoptosis is an active process that produces no inflammation, can be physiological and involves the rapid phagocytosis of apoptotic bodies. Necrosis, on the other hand, is an always pathological, non-energy dependent process that often causes an inflammatory reaction and is slow to clear.

Mechanisms of Apoptosis

Apoptosis has to be regulated tightly, otherwise we would have too much or too little cell growth. Apoptosis can be triggered by two main types of stimuli: a positive trigger or withdrawal of a signal.

Receptor-Mediated Apoptosis

Receptor-mediated apoptosis involves positive triggers that ‘push’ the cell into apoptosis. The binding of Tumour Necrosis Factor (TNF) to a cell surface receptor as well as the binding of Fas-ligand to the Fas receptor are examples of these kinds of stimuli.

These signals are transferred via intermediate proteins such as the TNF-Receptor-Associated-Death-Domain (TRADD) and the Fas-Associated-Death-Domain (FADD). This signal is then passed by the Death-Inducing-Signalling-Complex (DISC) and this activates the enzymes Caspase 8 and Caspase 3.

Caspase 3 acts on different components within the cell and also activates a Caspase-activated DNAse (shortened to CAD) which goes and breaks the DNA into 200 base pair segments. An inhibitory molecule known as ICAD regulates the CAD DNAse.

Non-Receptor Mediated Apoptosis

Apoptosis may also be initiated in a cell in response to a withdrawal of a trophic substance, by damage from irradiation or from hypoxia.

The permeability of the mitochondria is controlled by bcl-2 (which is anti-apoptotic) and bax (which is pro-apoptotic). Increased permeability in the mitochondria leads to the release of cytochrome C in the cytoplasm. This activates Caspase 9 with the help of Apaf-1 (pro-apoptotic Protease-Activating Factor). Caspase 9 then goes on to activate Caspase 3 and the pathway continues in a similar way to that of receptor mediated apoptosis. That is, Caspase 3 activates CAD which breaks the DNA up into regularly sized pieces.