Apoptosis I week 5

Apoptosis

Programmed cell death; a highly ordered, ATP-dependent process for eliminating damaged or unwanted cells without causing inflammation.

Apoptotic Bodies

Membrane-bound vesicles containing fragmented cellular contents that are quickly engulfed by macrophages.

Caspases

A family of cysteine proteases (Cys-Asp-ase) that are the executioners of apoptosis by cleaving target proteins after aspartate residues.

Initiator Caspases

The first caspases to be activated (e.g., Caspase-8, -9, -10); they activate the Effector Caspases.

Effector (Executioner) Caspases

Caspases (e.g., Caspase-3, -6, -7) that carry out the mass destruction of the cell's components.

Intrinsic Pathway (Mitochondrial)

The major apoptotic pathway triggered by internal stresses like DNA damage, leading to the release of Cytochrome c from the mitochondria.

Cytochrome c

A pro-apoptotic factor released from the mitochondrial intermembrane space; it binds to Apaf-1 to form the Apoptosome.

Apoptosome

A large protein complex formed by Apaf-1 and pro-Caspase-9 in the cytosol, which leads to Caspase-9 activation.

Smac/Diablo

A protein released from the mitochondria that binds to and inhibits IAPs (Inhibitor of Apoptosis Proteins) to allow caspases to function.

Bcl-2 Family

Regulatory proteins that control mitochondrial membrane permeability; includes pro-survival (Bcl-2, Bcl-XL) and pro-apoptotic (Bax, Bak, BH3-only) members.

Bax and Bak

Pro-apoptotic effector proteins that oligomerize on the outer mitochondrial membrane (OMM) to form pores, releasing Cytochrome c.

BH3-only proteins (e.g., PUMA, Noxa)

Pro-apoptotic sensor proteins that are activated by stress (often by p53) to inhibit pro-survival Bcl-2 proteins and activate Bax/Bak.

Phosphatidylserine Flip

The movement of phosphatidylserine from the inner to the outer leaflet of the plasma membrane during apoptosis, detected by Annexin V staining.

TUNEL Assay

TdT-mediated dUTP Nick End Labeling; a technique used to detect the cleaved DNA ends (oligonucleosomes) characteristic of apoptosis.

Necrosis

A form of cell death triggered by damage or ischemia that causes the cell to swell and burst (lysis), releasing contents and triggering an inflammatory response.

DNA Oligonucleosomes

The characteristic ladder-like fragments of genomic DNA created during apoptosis by the cleavage of DNA between nucleosomes by an activated DNAse.

PARP (Poly(ADP-ribose) polymerase)

A key nuclear protein involved in DNA repair that is one of the many substrates cleaved by activated Caspase-3, serving as a common detection assay for apoptosis.

Dye Exclusion Assay (e.g., Trypan Blue)

A simple assay that uses dyes to determine if a cell's plasma membrane is intact (alive) or ruptured (dead), but cannot distinguish between apoptotic death and necrotic death.

IAPs (Inhibitors of Apoptosis Proteins)

Endogenous regulators that suppress apoptosis by directly binding to and inhibiting caspases; some also act as E3-ubiquitin ligases to target pro-caspases for degradation

Smac/Diablo

A pro-apoptotic factor released from the mitochondria that binds to IAPs, thereby relieving the IAP-mediated inhibition of caspases and promoting apoptosis.

Omi-2

A pro-apoptotic factor released from the mitochondria along with Cytochrome C and Smac/Diablo.

BIR Domains (Baculovirus IAP Repeats)

Conserved subdomains (BIR1, BIR2, BIR3) found on IAP proteins that are crucial for binding and inhibiting caspases.

RING Domain (on IAPs)

A domain on IAPs that enables them to interact with the ubiquitin machinery, tagging pro-caspases for degradation by the proteasome.

Bcl-2

The first identified member of the family, originally found as a proto-oncogene in follicular B-cell lymphoma due to a translocation that caused its overexpression, preventing cell death.

Bax/Bak Oligomerization

The process where pro-apoptotic Bax and Bak proteins form multi-unit channels/pores in the Outer Mitochondrial Membrane (OMM), leading to the release of Cytochrome c and other factors.

Transmembrane Domains (Bcl-2)

Domains found on most Bcl-2 family proteins that anchor them to the Outer Mitochondrial Membrane (OMM), Endoplasmic Reticulum (ER), and Nuclear Envelope (NE).