#CancerResearch

Definition : Apoptosis is the process of programmed cell death.

Use : Helps the body get rid of unwanted cells.

When : Throughout life, from fetal development to old age.

• Cell death can be defined as an “irreversible degeneration of vital cellular functions culminating in the loss of cellular integrity (permanent plasma membrane permeabilization or cellular fragmentation).”

• The two main types of cell death are accidental cell death and regulated cell death. 

• Uncontrolled cell death that occurs due to severe injury, such as chemical or mechanical damage

• A controlled process that occurs during various types of stresses

• RCD refers to the autonomous and orderly death of cells controlled by genes in order to maintain the stability of the internal environment.

• The two main types of programmed cell death are apoptosis and autophagy. 

• Autophagy, meaning “self-eating,” is an intracellular degradation process that allows cells to recycle damaged intracellular components to generate energy and provide building blocks to create new cellular structures.

• Apoptosis is the process of programmed cell death that occurs in multicellular organisms, allowing the body to eliminate unwanted or damaged cells.

• Apoptosis is a series of steps that lead to programmed cell death. The steps include: 

  • Cell shrinkage: The cell shrinks in size. 

  • Blebbing formation: The cell develops blebs, which increase in size over time. 

  • Chromatin condensation: Chromatin changes from a genetically active shape to a condensed form. 

  • Cytoskeleton collapse: The cytoskeleton breaks down. 

  • Nuclear envelope disintegration: The nuclear envelope breaks down. 

  • Apoptotic bodies form: The condensed chromatin is fragmented and packaged into apoptotic bodies. 

  • Cell is phagocytosed: Another cell swallows or clears away the apoptotic bodies. 

• Blebs are protrusions in the cell membrane that look like blisters. They are caused by a separation of the cytoskeleton from the plasma membrane.

• Apoptosis is generally classified into two main pathways: intrinsic and extrinsic, which dictate how cells undergo programmed cell death based on internal stress or external signals, respectively.

• During apoptosis, a cell shrinks primarily due to a loss of intracellular ions, particularly potassium (K+) ions, which leads to an osmotic movement of water out of the cell, causing it to decrease in volume; this process is often referred to as "apoptotic volume decrease" (AVD) and is considered a hallmark feature of programmed cell death.

• The primary mechanism involves the activation of ion channels that allow potassium ions to leak out of the cell, creating a concentration gradient that draws water molecules out with them. 

• In apoptosis, ion channels can be activated by various stimuli including changes in membrane potential, intracellular calcium concentration, mechanical stress, and the binding of specific ligands (like ATP), which can trigger the opening of the channel pore, leading to an influx or efflux of ions that ultimately contribute to the cell death process

• Influx is the movement of something into a cell, while efflux is the movement of something out of a cell.

• During apoptosis, blebs form when the cell's cytoskeleton breaks down, causing the plasma membrane to detach from the underlying actin cortex, leading to outward bulges on the cell surface due to increased internal pressure generated by the actomyosin contractile machinery; these bulges can eventually detach from the cell as apoptotic bodies, effectively "blebbing" the cell membrane as a key morphological feature of late-stage apoptosis.

• Cytoskeleton disruption: The primary mechanism behind blebbing is the breakdown of the actin cytoskeleton, which normally provides structural support to the cell membrane. 

• Actomyosin contraction: The contractile force driving bleb formation is generated by the actomyosin complex, where myosin filaments slide along actin filaments, causing localized pressure on the cell membrane. 

• The caspase-3-activated protein Acinus is required for chromatin condensation. Condensed chromatin is fragmented by a nuclease called Caspase-Activated DNase (CAD). 

• In apoptosis, Acinus is a protein that is activated by caspase-3 cleavage. 

• Caspase-3 cleavage, which is crucial for apoptosis, is activated by upstream initiator caspases like caspase-8 or caspase-9, which cleave the procaspase-3 molecule at specific sites, transforming it into its active form; this process is triggered by apoptotic signals received by the cell through either the extrinsic (death receptor) or intrinsic (mitochondrial) pathway, essentially initiating a cascade of caspase activation leading to cell death.

• Procaspase-3: Before activation, caspase-3 exists as an inactive precursor called procaspase-3. 

• Initiator caspases: Caspase-8 (extrinsic pathway) or caspase-9 (intrinsic pathway) are the primary initiator caspases that cleave procaspase-3 to activate it.

• During apoptosis, the cytoskeleton collapses primarily due to the cleavage and degradation of its components, particularly actin filaments, by caspases, a family of proteases activated during the apoptotic process; this breakdown disrupts the structural integrity of the cytoskeleton, leading to the characteristic cell shrinkage and morphological changes observed in apoptotic cells. 

• During apoptosis, the nuclear envelope breaks down due to the activation of caspases, which are enzymes that cleave and degrade key proteins of the nuclear lamina, leading to the disruption of the nuclear structure and ultimately the fragmentation of the nucleus; this process involves the cleavage of nuclear pore complex proteins, causing increased permeability of the nuclear envelope and allowing the entry of apoptotic factors into the nucleus. 

• Nuclear lamina disruption: The nuclear lamina, a protein network that supports the nuclear envelope, is critical for its structural integrity; its breakdown by caspases leads to the collapse of the nuclear envelope. 

• Nuclear pore complex disruption: Caspases also cleave components of the nuclear pore complex, increasing the permeability of the nuclear envelope, allowing the diffusion of apoptotic factors into the nucleus.