Apoptosis: Role in Removing Damaged Cells

Questions and Answers

What is the primary function of apoptosis in response to excessive DNA damage?

To induce mutations in the DNA

To increase cell proliferation

To prevent the possible development of cancer (correct)

To repair damaged DNA through NER pathway

What is the consequence of thymine dimers on DNA structure?

It disrupts DNA structure and interferes with accurate replication (correct)

It has no effect on DNA structure

It enhances DNA replication accuracy

It increases DNA repair efficiency

What is the characteristic morphological change in cells during apoptosis?

Cell size increases

Nuclear envelope remains intact

Cytoskeleton collapses and cell surface bulges (correct)

Chromatin remains dispersed

What is the fate of apoptotic bodies?

They are engulfed and destroyed by phagocytosis Signup and view all the answers

What triggers the activation of caspases during apoptosis?

Cleavage of initiator caspases Signup and view all the answers

What is the role of executor caspases in apoptosis?

They activate changes in cell biology observed in apoptosis Signup and view all the answers

What is the consequence of excessive DNA damage on skin keratinocytes?

They form 'sunburn cells' and undergo apoptosis Signup and view all the answers

What is the characteristic of apoptosis in terms of its duration?

It is a rapid process with few dead cells observed Signup and view all the answers

What is the primary function of phosphatidylserine in the process of apoptosis?

It is a marker for phagocytosis Signup and view all the answers

Which of the following proteins is involved in blocking apoptosis?

Bcl2 Signup and view all the answers

What is the role of survival factors in apoptosis?

They block apoptosis by binding to cell surface receptors Signup and view all the answers

What is the consequence of cells not receiving continuous signaling from survival factors?

Apoptosis is triggered Signup and view all the answers

What is the relevance of the apoptosis regulation mechanism in development?

It is involved in the adjustment of the number of nerve cells Signup and view all the answers

What is the function of caspases in the process of apoptosis?

They stimulate the flipping of phosphatidylserine to the outer leaf of the plasma membrane Signup and view all the answers

What is the primary function of p53 in the intrinsic pathway to trigger apoptosis?

To stimulate the aggregation of Bax and Bak in the mitochondrial membrane Signup and view all the answers

What is the result of mitochondrial outer membrane permeabilization (MOMP)?

The release of cytochrome c from the mitochondria Signup and view all the answers

What is the primary function of executioner caspases in the apoptosis process?

To degrade iCAD and allow CAD to fragment DNA Signup and view all the answers

What is the primary function of the apoptosome complex?

To recruit and activate initiator caspases Signup and view all the answers

What is the result of DNA fragmentation by CAD in the apoptosis process?

A ladder of DNA fragments Signup and view all the answers

What is the consequence of DNA damage in the intrinsic pathway to trigger apoptosis?

The stimulation of the p53 pathway and subsequent activation of Bax and Bak Signup and view all the answers

What is the function of the death-inducing signalling complex (DISC) in apoptosis?

To activate initiator caspases and trigger apoptosis Signup and view all the answers

What is the role of Bax and Bak in the intrinsic pathway to trigger apoptosis?

To allow for mitochondrial outer membrane permeabilization (MOMP) Signup and view all the answers

What is the ultimate consequence of the intrinsic pathway to trigger apoptosis?

The triggering of the caspase cascade and subsequent cell death Signup and view all the answers

What is the primary mechanism of apoptosis triggered by cytotoxic T-cells?

The extrinsic pathway of apoptosis triggered by Fas ligand Signup and view all the answers

What is the role of iCAD in the apoptosis process?

To inhibit the activity of CAD Signup and view all the answers

What is the function of death receptors in the apoptosis process?

To trigger apoptosis through the extrinsic pathway Signup and view all the answers

What is the result of the activation of initiator caspases in the apoptosis process?

The activation of executioner caspases Signup and view all the answers

What is the characteristic pattern of DNA fragmentation observed in apoptosis?

A ladder of DNA fragments Signup and view all the answers

What is the primary reason why apoptosis does not occur in necrosis?

The circumstances occur too suddenly for apoptosis to occur. Signup and view all the answers

Which of the following is NOT a characteristic of necrosis?

Programmed cell death with a controlled release of cellular contents Signup and view all the answers

What is the role of RIPK1/RIPK3 in necroptosis?

Phosphorylation of MLKL to trigger its oligomerization Signup and view all the answers

What is the primary difference between necrosis and necroptosis?

Necrosis is uncontrolled, while necroptosis is a programmed form of cell death Signup and view all the answers

What is the outcome of the phosphorylation of MLKL in necroptosis?

Formation of a ion channel in the plasma membrane Signup and view all the answers

What is the outcome of the binding of death ligands to death receptors in necroptosis?

Triggering of the necroptosis pathway via serine/threonine kinases Signup and view all the answers

Study Notes

Role of Apoptosis in Removing Damaged Cells

Apoptosis removes damaged cells to prevent cancer development
Exposure to UVB (290-320nm) leads to thymine dimers, disrupting DNA structure and causing mutations
Thymine dimers are usually repaired by the Nucleotide Excision Repair (NER) pathway
If DNA damage is excessive, apoptosis removes the cell to prevent cancer development

Morphological Changes During Apoptosis

Cells become smaller
Cytoskeleton collapses
Nuclear envelope disassembles
Chromatin condenses and is fragmented
Cell surface bulges (blebs)
Cells break up into membrane-bound "apoptotic bodies"
Apoptotic bodies are engulfed and destroyed by phagocytosis by macrophages
Apoptosis is a rapid process, with few dead cells observed in tissue

Caspases – Intracellular Mediators of Apoptosis

Caspases are a family of proteases that trigger a sequence of intracellular events during apoptosis
Caspases are synthesized as inactive precursors that are activated by cleavage during apoptosis
Initiator caspases are activated by dimerization and cleavage, then activate executor caspases
Executor caspases activate all the changes in cell biology observed in apoptosis

DNA Fragmentation

Executioner caspases activate a specific endonuclease, CAD, which fragments DNA into discrete chunks
DNA fragmentation occurs between nucleosomes, resulting in a ladder of fragments

Extrinsic Pathway to Trigger Apoptosis

Apoptosis can be triggered from outside the cell through activation of death receptors on the cell surface
Binding of Fas ligand to the Fas receptor activates the caspase cascade
Death receptors are part of the tumour necrosis factor (TNF) family of receptors

Intrinsic Pathway (Mitochondrial) to Trigger Apoptosis

The intrinsic pathway is activated in response to DNA damage, detected via the p53 pathway
p53 stimulates the aggregation of Bax and Bak in the mitochondrial membrane, leading to mitochondrial outer membrane permeabilization (MOMP) and cytochrome c release
Cytochrome c binds to Apaf1 to form the apoptosome complex, which recruits initiator caspases and triggers the caspase cascade

Removal of Apoptotic Cell by Macrophage

Cells undergoing apoptosis are detected and removed by phagocytosis
Phosphatidylserine (PS) is flipped to the outer leaf of the membrane, which is detected and triggers phagocytosis

Survival Factors Block Apoptosis

Some proteins, such as Bcl2, interfere with Bax/Bak aggregation and block apoptosis
Most cells require continuous signaling by survival factors produced by neighboring cells that block apoptosis
Survival factors bind to cell surface receptors, leading to the synthesis of Bcl2

Necrosis – Cell Death with Collateral Damage

Necrosis occurs in response to a dramatic event, such as hypoxia, ischemia, high temperature, or chemical exposure
Cells swell (oncosis) and the membrane becomes leaky and breaks, releasing contents and triggering an inflammatory response

Other Mechanisms of Cell Death: Necroptosis

Necroptosis is a programmed form of necrosis that occurs through the binding of death ligand to death receptor
The necroptosis pathway involves receptor interacting protein kinase 1 (RIPK1) and RIPK3, leading to the formation of an ion channel in the plasma membrane
The cell then swells and breaks, resulting in cell death

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Description

Learn about the process of apoptosis, how it removes damaged cells to prevent cancer development, and the morphological changes that occur during apoptosis.