There are two ways in which the body’s cells undergo cell death: necrosis or apoptosis.
Necrosis is usually caused by cell injury, whereas apoptosis is more tightly regulated
and initiated by specific triggers.
Let’s take a closer look at the main characteristics of each and their different roles.
Necrosis is caused by cell injury and disrupts cellular function.
For example, necrosis occurs in cardiac cells during a heart attack as a result of decreased
blood flow and oxygen.
Damage to the cell impairs energy production, disabling cells to control their fluid and
ion balance.
As a result, the cell starts to swell.
Other organelles such as lysosomes also swell, leading to lysosomal membrane damage.
Lysosomal enzymes then leak out of the cell and into the cytoplasm.
This influx of degrading enzymes subsequently breaks down other cell organelles.
In the nucleus, the DNA is degraded, which is visible as chromatin clumping.
The nucleus shrinks and eventually dissolutes, a process known as karyolysis.
The cell eventually loses its integrity with membrane blebbing and leakage of cell content.
This leakage often elicits inflammation and calls for the action of bystander immune cells.
Similar to necrosis, cell degradation during apoptosis follows a distinct pattern; however,
the process by which cell organelles degrade is more tightly controlled.
Therefore, apoptosis is often referred to as programmed cell death.
Let’s take a closer look at apoptosis.
Apoptosis can be initiated by two different pathways: the intrinsic or the extrinsic pathway.
The intrinsic pathway is regulated by proteins from the Bcl family, which contain pro-apoptotic
and anti-apoptotic members.
The body’s cells have chemical sensors that react to cell damage.
Once activated, there is a shift in the balance between pro-apoptotic and anti-apoptotic proteins
towards apoptosis.
The result is activation of the proteins Bax and Bak, which form pores in the mitochondrial
membrane, leading to a subsequent release of cytochrome c.
Cytochrome C is a molecule attached to the inner mitochondrial membrane and is part of
the electron transport chain.
Once released from the mitochondria, cytochrome c activates caspases, a class of protein degrading
enzymes that are actual mediators of cell death.
Because of the role of the mitochondria and the release of cytochrome c, the intrinsic
pathway of apoptosis is also termed the mitochondrial pathway.
The second pathway, the extrinsic pathway, is initiated by receptors on the cell surface
such as the FAS receptor.
FAS, or first apoptotic signal, is aptly termed the death receptor.
The FAS receptor can be activated by other cells such as cytotoxic T cells, which have
a ligand for FAS, or by messenger molecules such as tumor necrosis factor.
Once activated, it initiates a cascade that also results in the activation of caspases
and subsequent cell degradation.
Activation of caspases leads to the degradation of the cytoskeleton and triggers nuclear enzymes
called endonucleases.
Endonucleases cleave the DNA, resulting in nuclear fragmentation.
In addition to DNA, other cell organelles are also digested by caspases.
The cell starts to shrink and separates into smaller fragments termed apoptotic bodies.
Apoptotic bodies are phagocytosed by macrophages and further degraded.
The cell membrane remains intact during apoptosis and there is no leakage of cell content.
Therefore, unlike necrosis, apoptosis does not elicit inflammation.
Apoptosis can occur under physiological conditions, such as the removal of unwanted cells during
embryogenesis.
It can also occur as a response to cell injury such as DNA damage, in cases where the cell
remains capable of activating the cell death program.
If there is severe damage and the cell lacks the energy to undergo organized degradation,
it can shift from apoptosis to necrosis.