Why Lysosomes are called "Suicidal Bags of the Cell"?

 

Why are Lysosomes called "Suicidal Bags of the Cell"?

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Introduction –

Lysosomes are membrane-bound organelles found within eukaryotic cells, involved in cellular catabolism, recycling, and signalling. Often referred to as the "digestive system" of the cell, they contain a large array of over 50 acid hydrolases, including proteases, nucleases, glycosidases, lipases, and phosphatases. These enzymes are optimally active at the acidic pH (approximately 4.5-5.0) kept within the lysosomal lumen by a vacuolar H+-ATPase (proton pump) in the lysosomal membrane. This acidic environment is necessary for efficient degradation of various biological polymers, including proteins, nucleic acids, carbohydrates, and lipids.

Fig.1 Structure of lysosome

Lysosomes as the Suicidal Bags of the Cell -

The term "suicidal bags of the cell" for lysosomes was first coined by Christian de Duve. It is because of their potent destructive capabilities and their role in programmed cell death.

Potent Hydrolytic Enzymes and Autolysis:

• Lysosomes contain a strong array of about 50 different acid hydrolases. These enzymes are capable of breaking down almost all types of biological macromolecules – proteins, nucleic acids, lipids, and carbohydrates – into their simpler components.

• The crucial factor is that these enzymes are highly active in the acidic environment within the lysosome (pH 4.5-5.0), a pH that is considerably lower than the neutral pH of the cell's cytoplasm (approximately 7.2).

• The lysosomal membrane acts as a strong barrier under normal, healthy cellular conditions thus, safeguarding these destructive enzymes and preventing them from accessing and degrading vital cytoplasmic components.

• However, if this membrane structur is disturbed, for instance, if due to severe cellular damage, infection, or high stress, the lysosomal membrane can rupture. This rupture results in the unregulated release of these powerful hydrolytic enzymes into the cytoplasm.

• Once in the cytoplasm, even though the pH is not optimal for their activity, many of these enzymes can still keep sufficient activity to begin destroying the cell's own proteins, organelles, and other cellular contents. This process of self-digestion is known as autolysis (auto-self,  lysis-breakdown).

Function in Programmed Cell Death (Autophagic Cell Death):

• While autolysis shows an uncontrolled, often pathological, form of cell death, lysosomes also play a more controlled and active role in certain forms of programmed cell death (PCD), especially autophagic cell death.

• Programmed cell death is a fundamental biological process vital for development, tissue homeostasis, and the elimination of damaged or unwanted cells. Apoptosis is the most well-known form of PCD.

• In autophagic cell death, excessive or uncontrolled autophagy (the cell's self-eating process where lysosomes degrade cellular components) can lead to the death of the cell. While autophagy is actually a survival mechanism, allowing cells to recycle components during nutrient deprivation or stress, if the autophagic flux becomes too high or if the cell cannot compensate for the extensive degradation, it can lead to cellular demise.

• In these contexts, lysosomes are not merely passive recipients of degrading material but active participants in the signalling pathways that orchestrate cell death. Lysosomal membrane permeabilization (LMP), where lysosomal contents leak into the cytoplasm, is a key event that can initiate or amplify various cell death programs, including those with features of both apoptosis and necrosis, collectively referred to as lysosomal cell death (LCD).

In conclusion, the word "suicidal bags" highlights the following points:

• Destructive Potential: The extreme destructive power of the lysosomal acid hydrolases.

• Containment: The important role of the lysosomal membrane in storing these enzymes and protecting the cell.

• Self-Destruction: The consequence of lysosomal membrane rupture, leading to the rapid and irreversible death i.e. self-digestion (autolysis) of the cell.

• Controlled Demise: Their active, though sometimes contradictory, role in regulated cell death routes beyond simple accidental rupture.