Types of Cell Death

Apoptosis

Apoptosis is a programmed cell death (Carvalho and Villar, 2018). It has characteristic morphological alterations that can be viewed under a microscope. These alterations include:

· Cellular shrinkage

· Pyknosis (chromatin condensation)

· Karryhorexis (nuclear fragmentation)

· Plasma membrane blebbing

· Apoptotic body formation (Carvalho and Villar, 2018).

The apoptotic bodies that are formed are engulfed quickly by the surrounding macrophages so that there is not inflammatory response to the dying cell (Carvalho and Villar, 2018).

Apoptosis can follow an intrinsic or extrinsic pathway. The intrinsic pathway is driven by intracellular signals such as DNA damage and metabolic alterations (Carvalho and Villar, 2018). It is a functional consequence of mitochondrial membrane disturbances and release of cytochrome c, which forms a apoptosome in the cytoplasm of the cell (Creative Diagnostics, 2020). The apoptosome with apoptotic protease activating factor 1 (APAF1) and inactive caspase-9 hydrolyses adenosine triphosphate (ATP) to cleave and activate caspase-9 (Creative Diagnostics, 2020). Caspase-9 then cleaves and activates executioner caspases (3, 6, 7), ultimately leading to cell death (Creative Diagnostics, 2020).

The extrinsic pathway is driven by extracellular signals such as death ligands (Carvalho and Villar, 2018). The death receptors include Fas receptors, tumour necrosis factor (TNF) receptors, and TNF-related apoptosis-inducing ligand (TRAIL) receptors (Creative Diagnostics, 2020). These receptors interact with proteins in the cytoplasm that ultimately leads to a DEATH domain protein, which recruits caspase-8 and leads to cellular apoptosis (Creative Diagnostics, 2020).

Autophagy

Autophagy is a cellular recycling process (Parzych and Klionsky, 2014) and regulatory mechanism for cells (Carvalho and Villar, 2018). Its function is to maintain cellular homeostasis and protect cellular homeostasis (Carvalho and Villar, 2018). The process it uses is through the lysosomal pathway, where lysosomes prevent the accumulation of aggregated and misfolded proteins and preventing the functioning of damaged organelles (Carvalho and Villar, 2018). Following autophagy is autophagic cell death, where the chromotin does not condense like in apoptosis but there is large-scale autophagic vacuolization of the cellular cytoplasm (Kroemer, 2008).

Necrosis

Necrosis was originally not considered a regulated cellular death, but this has changed as more research has been done on the process. Necrosis is caused by loss of membrane integrity, intracellular organelle swelling and ATP depletion (Niemann and Rohrbach, 2016). The typical characteristics seen in necrosis include:

· Organelle swelling

· Plasma membrane rupture

· Cell lysis

· Loss of intracellular content (Carvalho and Villar, 2018).

This last point is the reason that, unlike autophagy and apoptosis, necrosis is an inflammatory condition.

References

Carvalho, H. and Villar, R., 2018. Radiotherapy And Immune Response: The Systemic Effects Of A Local Treatment. [online] NCBI. Available at: <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6257057/> [Accessed 30 March 2020].

Creative-diagnostics.com. 2020. Intrinsic Apoptosis Pathway. [online] Available at: <https://www.creative-diagnostics.com/intrinsic-apoptosis-pathway.htm> [Accessed 30 March 2020].

Creative-diagnostics.com. 2020. Extrinsic Apoptosis Pathway. [online] Available at: <https://www.creative-diagnostics.com/extrinsic-apoptosis-pathway.htm> [Accessed 30 March 2020].

Guido Kroemer, B., 2008. Autophagic Cell Death: The Story Of A Misnomer. [online] PubMed Central (PMC). Available at: <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727358/> [Accessed 30 March 2020].

Niemann, B. and Rohrbach, S., 2016. Metabolically Relevant Cell Biology – Role Of Intracellular Organelles For Cardiac Metabolism. [online] Science Direct. Available at: <https://www.sciencedirect.com/science/article/pii/B9780128023945000030> [Accessed 30 March 2020].

Parzych, K. and Klionsky, D., 2014. An Overview Of Autophagy: Morphology, Mechanism, And Regulation. [online] NCBI. Available at: <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894687/> [Accessed 30 March 2020].