Apoptosis and Cell Death Mechanisms

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Questions and Answers

What is the role of phosphatidylserine in apoptotic cells?

It serves as a marker for phagocytosis by macrophages. (correct)

It maintains the mitochondrial membrane potential.

It induces inflammation in neighboring cells.

It supports ATP production.

What is a primary characteristic of caspases in the apoptosis process?

They have a cysteine at the active site. (correct)

They are activated by oxidative stress.

They cleave at specific serine residues.

They are produced as active enzymes.

During apoptosis, what happens to the chromosomal DNA?

It enhances the gene expression of survival genes.

It remains intact and functional.

It becomes hypermethylated.

It is cleaved into fragments of distinct sizes. (correct)

What triggers the activation of procaspases in the apoptosis cascade?

Proteolytic cleavage of procaspases. Signup and view all the answers

What occurs to the mitochondrial membrane potential during apoptosis?

It is lost, leading to a release of cytochrome C. Signup and view all the answers

What is the primary role of apoptosis in adult tissues?

To eliminate abnormal or nonfunctional cells Signup and view all the answers

Which characteristic morphological change is associated with apoptosis?

Nuclear chromatin fragmentation Signup and view all the answers

What term describes the controlled cell death process in which cells kill themselves?

Programmed cell death Signup and view all the answers

How does the cell surface change during apoptosis?

It becomes chemically altered for macrophage recognition Signup and view all the answers

What does the term 'apoptotic bodies' refer to?

Fragments formed from large apoptotic cells Signup and view all the answers

During animal development, apoptosis is crucial for which of the following processes?

Sculpting hands and feet Signup and view all the answers

What does the term 'falling off' refer to in the context of apoptosis?

The Greek origin of the word apoptosis Signup and view all the answers

Which statement accurately describes the biochemical changes in apoptotic cells?

They show characteristic biochemical changes for identification Signup and view all the answers

What is the role of the caspase recruitment domain (CARD) in initiator procaspases?

To enable assembly with adaptor proteins into activation complexes Signup and view all the answers

Which of the following describes the process of procaspase activation?

Procaspases form a heterodimer when cleaved Signup and view all the answers

What happens after initiator procaspases are activated?

They activate executioner procaspases Signup and view all the answers

Which of the following cleaves target proteins leading to controlled cell death?

Executioner caspases Signup and view all the answers

Which of the following proteins is NOT typically cleaved by executioner caspases?

Transcription factors Signup and view all the answers

What are the two main pathways that activate the caspase cascade leading to apoptosis?

Extrinsic and intrinsic pathways Signup and view all the answers

Which initiator procaspase is commonly associated with the intrinsic pathway?

Caspase-9 Signup and view all the answers

Which of the following statements about caspases is true?

Some caspases are involved in inflammatory processes Signup and view all the answers

What is the initial signal that activates the extrinsic pathway of apoptosis?

Fas ligand binding to Fas death receptors Signup and view all the answers

Which component of the Fas death receptor is crucial for initiating apoptosis?

Intracellular death domain Signup and view all the answers

What role does the adaptor protein FADD play in the extrinsic pathway?

It recruits initiator procaspases to form a complex. Signup and view all the answers

What happens within the death-inducing signaling complex (DISC)?

Procaspases are activated through proximity-induced cleavage. Signup and view all the answers

Which of the following describes a mechanism that inhibits the extrinsic pathway of apoptosis?

Decoy receptors lacking a death domain Signup and view all the answers

Which type of cellular response can lead to the activation of the intrinsic pathway rather than the extrinsic pathway?

Injury to the cell Signup and view all the answers

What does the FLIP protein resemble and how does it function in inhibiting apoptosis?

Initiator procaspase; competes for binding sites Signup and view all the answers

What is a function of activated caspase-8 and caspase-10 in the cascade leading to apoptosis?

Activate executioner procaspases Signup and view all the answers

What initiates the intrinsic pathway of apoptosis?

Binding of cytochrome c to Apaf1 Signup and view all the answers

What is the role of BH123 proteins in the intrinsic pathway?

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

How do BH3-only proteins contribute to apoptosis?

They neutralize anti-apoptotic Bcl2 proteins Signup and view all the answers

What is the consequence of cytochrome c being released from the mitochondria?

Initiation of the apoptosome formation Signup and view all the answers

What is a characteristic of anti-apoptotic Bcl2 proteins?

They inhibit BH123 proteins in the absence of an apoptotic stimulus Signup and view all the answers

What structure is formed when Apaf1 oligomerizes upon cytochrome c binding?

Apoptosome Signup and view all the answers

Which proteins are considered pro-apoptotic in the context of the intrinsic pathway?

Bax and Bad Signup and view all the answers

Study Notes

Apoptosis

Cell death is vital for animal and plant development, continuing into adulthood.
In a healthy adult human, billions of cells die every hour in the bone marrow and intestines.
Tissue size remains consistent as cell division balances cell death.
Normal cell death is a form of cellular suicide.
Cells undergo a controlled death process called programmed cell death.

Apoptosis: Definition

Apoptosis is the main type of programmed cell death.
It originates from the Greek word meaning "falling off."
Apoptotic cells have altered cell surfaces, enabling rapid engulfment by macrophages before spillage of their contents.
This protects against damaging inflammation.

Apoptosis: Morphology

Apoptotic cells display distinctive morphological changes.
Cells shrink and condense.
Cytoskeleton structure disintegrates.
Nuclear chromatin condenses and breaks into fragments.
Large cells often fragment into membrane-bound apoptotic bodies.
Cell surface or apoptotic bodies' chemistry alters.

Apoptosis: Classical Examples

Crucial in animal development for shaping structures like hands and feet, and regulating nervous system cells.
Contributes to the development of adaptive immune system components.
In metamorphosis, eliminating unnecessary cells.
In adult tissues, removing malfunctioning or dangerous cells.
Essential for eliminating cells no longer needed following infections.
Maintains a ready pool of short-lived immune cells, like neutrophils in bone marrow.

Apoptosis: Biochemistry

Biochemical changes help identify apoptotic cells.
During apoptosis, endonuclease fragments DNA into unique sizes.
These DNA fragments form a characteristic "ladder" pattern in gel electrophoresis.
Phosphatidylserine, a negatively charged phospholipid, moves from the inner to the outer leaflet of the cell membrane, acting as a marker for engulfment.
Loss of transmembrane potential in mitochondria, releasing cytochrome c.

Apoptosis Machinery

Apoptosis relies on a family of caspase proteases.
Caspases have a cysteine at their active site and cleave aspartic acid residues.
Caspases are initially inactive precursors (procaspases).
Proteolytic cleavage activates them.

Apoptosis: The Beginning

Healthy cells constantly produce procaspases.
Procaspase activation requires an initiating trigger.
Initiator procaspases contain a prodomain with a caspase recruitment domain (CARD).
CARDs allow assembly with adaptor proteins and activation complexes when required.
Once initiator procaspases are close together, they activate each other, making the process irreversible.

Procaspase Activation

Procaspases have large and small subunits.
Subunits form a heterodimer that then combines with another to make a functional active tetramer.
The first activated procaspases are initiator procaspases, activating subsequent executioner procaspases.
Executioner caspases cleave essential proteins in the cell, leading to its demise.

Not all caspases mediate apoptosis

Some caspases play roles in inflammation.
Caspases involved in apoptosis fall into initiator (e.g., caspase 8, 9) and executioner (e.g., caspase 3, 7) groups.

Target Proteins

Executioner caspases cleave target proteins, affecting the nuclear lamina, endonucleases, cytoskeleton, and cell-cell adhesion proteins.

Signaling Pathways (Extrinsic)

Cell surface Fas death receptors trigger the extrinsic pathway.
They belong to the TNF receptor family.
Receptors are homotrimers with extracellular ligand-binding domains, a transmembrane domain, and intracellular death domains.
They are activated by external signals.

Signaling Pathways (Intrinsic)

Intrinsic pathways are activated by internal stimuli, such as DNA damage, lack of oxygen, or nutrient deprivation.
Mitochondria release cytochrome c, initiating the intrinsic pathway through the activation of Apaf1.
Apaf1 binds with cytochorome c and procaspase-9 to form the apoptosome.

Regulation Intrinsic Pathway

Bcl2 proteins tightly control the intrinsic pathway.
Different Bcl2 family members regulate the balance between apoptosis and survival.
Pro-apoptotic members (BH123) instigate apoptosis upon activation.
Anti-apoptotic (e.g., Bcl2) members prevent apoptosis.
BH3-only proteins are a crucial regulatory link between anti- and pro-apoptotic Bcl2 proteins.

Regulation Intrinsic Pathway IAPs

IAPs (inhibitors of apoptosis) are proteins that prevent excessive apoptosis.
They bind to and inhibit activated caspases, preventing uncontrolled processes.
Anti-IAPs are also present and can overcome this inhibition for programmed cell death.

Extracellular Survival Factors

Survival factors can either inhibit or facilitate apoptosis, in large part from their interactions with intracellular molecules and pathways.

Summary

Inappropriate apoptosis can contribute to various diseases.
Imbalances in apoptosis, either too much or too little, significantly impact the body's health.
Different cell death pathways control excessive or deficient apoptosis across the human body.

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Description

This quiz explores the fundamental concepts of apoptosis, including the roles of phosphatidylserine and caspases, changes in chromosomal DNA, and the significance of mitochondrial membrane potential. Test your knowledge on the morphological characteristics and implications of apoptosis in development and adult tissues.