Apoptosis

What is apoptosis?

It is a distinctive and important mode of programmed cell death.

Which form of cell death is analogized as "cellular harakiri" in the provided material?

Apoptosis.

In the development of a frog, what structure is eliminated via apoptosis during its metamorphosis from a tadpole?

The tail.

What specific biological process is responsible for sculpting the digits in a developing mouse paw?

Apoptosis, which removes the tissue between the digits.

What is the function of apoptosis in the formation of arthropod joints?

It is required to clear the connecting tissue to create functional joints.

What is the key difference between apoptotic and necrotic cells regarding their plasma membranes and effect on neighbouring cells?

Apoptotic cells have intact plasma membranes and die neatly, while necrotic cells spill their contents, damaging their neighbours.

The proteolytic cascade that mediates apoptosis depends on what family of enzymes?

Caspases (Cysteine Aspartate Proteases).

What does the name "caspase" stand for?

Cysteine Aspartate Proteases.

What type of amino acid do caspases cut proteins next to?

Aspartate amino acids.

Caspases are synthesized in an inactive precursor form known as _.

procaspases

How are inactive procaspases activated?

They are activated by cleavage at aspartic acids, often by other caspases.

What is the primary role of initiator caspases in the apoptotic program?

They begin the apoptotic program by activating the executioner caspases.

What is the primary role of executioner (effector) caspases?

They orchestrate the apoptosis program by cleaving multiple cell proteins.

According to the source material, which two caspases are examples of initiator caspases?

Caspase-8 and Caspase-9.

According to the source material, which three caspases are examples of executioner (effector) caspases?

Caspase-3, Caspase-6, and Caspase-7.

How do inactive initiator caspase monomers become activated?

They activate when an apoptotic signal causes them to dimerize and self-cleave.

How are inactive executioner caspase dimers activated?

They are cleaved and activated by initiator caspases.

The sequence of one caspase activating many others makes the apoptotic cascade both _ and irreversible.

amplifying

What is the name of the DNAse that is activated by a caspase to cleave DNA between nucleosomes?

CAD (Caspase-Activated DNAse).

What molecule inhibits CAD, and how is this inhibition removed during apoptosis?

iCAD (inhibitor of CAD) inhibits it; an active executioner caspase (like caspase-3) cleaves iCAD to release and activate CAD.

The characteristic pattern of DNA fragmentation during apoptosis, visible on a gel, is often referred to as a DNA _.

ladder

What are the two main activation pathways for apoptosis?

The extrinsic pathway (signalled from outside the cell) and the intrinsic pathway (signalled from inside the cell).

Which pathway is initiated by the activation of cell-surface death receptors?

The extrinsic pathway.

In the extrinsic pathway, what molecule on a killer lymphocyte binds to the death receptor on a target cell?

Fas ligand.

Binding of the Fas ligand to the Fas death receptor exposes what structures on the receptor tails?

Death domains.

What intracellular adaptor protein binds to the clustered death domains of the Fas receptor?

FADD (Fas-associated death domain).

The large structure formed by the Fas receptor, FADD, and initiator caspases is called the _.

DISC (death-inducing signaling complex)

Which initiator caspase is recruited to the DISC and activated by dimerization?

Caspase-8.

The intrinsic pathway of apoptosis is typically signalled from which organelle?

The mitochondrion.

What event is the key signal that activates the intrinsic pathway of apoptosis?

The release of cytochrome c from the mitochondria into the cytoplasm.

In the cytoplasm, what adaptor protein does cytochrome c bind to?

Apaf1 (apoptotic protease activating factor 1).

The binding of cytochrome c to Apaf1 causes Apaf1 to oligomerize into a large complex called the _.

apoptosome

What initiator caspase is recruited to the apoptosome and activated by dimerization?

Caspase-9.

What is the primary family of proteins that regulate the intrinsic pathway of apoptosis?

The Bcl2 family of proteins.

What is the function of pro-apoptotic Bcl2 proteins (e.g., Bak)?

They make holes in the mitochondrial outer membrane, allowing cytochrome c to escape.

What is the function of anti-apoptotic Bcl2 proteins (e.g., BclxL)?

They inactivate the pro-apoptotic Bcl2 proteins, blocking pore formation.

What is the function of IAPs (Inhibitors of Apoptosis proteins)?

They provide another line of defense by binding and preventing the activation of some procaspases.

What phospholipid acts as an "eat-me" signal when it appears on the outer surface of an apoptotic cell's plasma membrane?

Phosphatidylserine (PtdSer).

What type of enzyme, which is degraded by caspases during apoptosis, is normally responsible for keeping Phosphatidylserine on the inner side of the cell membrane?

A flippase.

Which model organism was crucial for the initial discoveries concerning the genetic regulation of programmed cell death?

C. elegans (nematode).

Sydney Brenner, John E. Sulston, and Robert Horvitz won the Nobel Prize for their discoveries in C. elegans related to organ development and what other process?

Programmed cell death.

Mutants in C. elegans with genes like ced-1 were isolated because they showed impaired clearance of what?

Apoptotic cells.

What is ferroptosis?

An intracellular iron-dependent form of cell death that is distinct from apoptosis and necrosis.

Ferroptosis is characterized by the accumulation of what type of damaged molecules?

Oxidatively damaged phospholipids (lipid peroxidation).

In the process of cell competition, what happens to cells with reduced fitness when surrounded by wild-type cells?

They are eliminated via apoptosis.

What is the role of the adaptor protein FADD in the extrinsic pathway?

It binds to the activated Fas death receptor and recruits initiator caspase-8.

What is the name of the domain on Apaf1 that is exposed upon binding cytochrome c and is responsible for recruiting caspase-9?

The CARD (caspase recruitment domain).