Apoptosis, what is apoptosis?
Apoptosis (from the Greek words apo = from and ptosis = falling,) is a process of programmed cell death. Cell death can be fundamentally divided into accidental cell death and programmed cell death. Programmed cell death is a genetically controlled cell-intrinsic suicide process that eliminates specific cells. It is essential for controlling cell number, removing unwanted diseased or damaged cells and maintaining the cellular homeostasis. ‘Apoptosis’ and programmed cell death’ are often used synonymously. Although apoptosis is the most common form of programmed cell death, there are also non-apoptotic programmed cell deaths such as autophagy and regulated necrosis.
Not all cell death is apoptotic. Cell death also occurs due to injury. When a cell is damaged to such an extent that it simply cannot survive, it is called unregulated necrosis. Term necrosis was earlier regarded as an unregulated mode of cell death. However, many recent studies reported the existence of regulated necrosis (termed necroptosis). Necroptosis is a regulated necrosis mediated by death receptors. Unregulated necrosis or simply necrosis is considered as an accidental and uncontrolled cell death. It is characterized by loss of cell membrane integrity and an uncontrolled release of cellular components into the extracellular space. This release initiates an inflammatory response attracting leukocytes and nearby phagocytes to eliminate the dead cells and its products by phagocytosis. In contrast, necroptosis shows morphological features similar to necrosis, but, as apoptosis, is strictly regulated. However, while apoptosis depends on caspase activation, necroptosis is negatively regulated by caspases and needs the intervention of the receptor-interacting protein (RIP) that is thought to be a necroptosis key mediator. It is conceivable that when the apoptotic caspases fail to be activated, then cells undergo necroptosis as an alternative death pathway.
Autophagy is an intracellular degradation process of cytoplasmic components through the formation of autophagosomes. The autophagosomes fuse with lysosomes. The resulting compartment, called autolysosome, causes enzymatic breakdown of the cytoplasmic components.
The demise of cells by apoptosis is marked by a well-defined sequence of morphological changes. Apoptosis exhibits cell shrinkage, chromatin condensation (pyknosis), nuclear fragmentation (karyorrhexis), and plasma membrane blebbing, culminating with the formation of apparently intact small vesicles (commonly known as apoptotic bodies) that are efficiently taken up by neighboring cells with phagocytic activity and degraded within lysosomes. Importantly, the intracellular constituents are not released into the extracellular milieu, where they would probably have deleterious effects on neighboring cells, but instead are phagocytosed by neighboring cells.
Chemical changes in the surface of apoptotic cells or bodies allow the surrounding cells or macrophages to recognize and engulf them. An especially important change occurs in the plasma membrane of apoptotic cells. The negatively charged phospholipid phosphatidylserine is normally exclusively located in the inner leaflet of the lipid bilayer of the plasma membrane, but it flips to the outer leaflet in apoptotic cells, where it can serve as a marker of these cells. There is essentially no inflammatory reaction associated with the process of apoptosis nor with the removal of apoptotic cells because:
- apoptotic cells do not release their cellular constituents into the surrounding interstitial tissue;
- they are quickly phagocytosed by surrounding cells and,
- the engulfing cells do not produce anti-inflammatory cytokines.