BIO 211 Lecture 6 Apoptosis

apoptosis

programmed cell death

• highly regulated and controlled

Necrosis

uncontrolled cell death

• cell loses structural integrity and explodes, exposing other cells to its signaling molecules and harmful contents

ATP

Reversible cell injuries:

1. reduced oxidative phosphorylation and depletion of —

2. Cellular swelling caused by changes in ion concentrations and water influx

3. Intracellular organelles begin to change in function and appearance

Swelling

Reversible cell injuries:

1. reduced oxidative phosphorylation and depletion of ATP

2. Cellular — caused by changes in ion concentrations and water influx

3. Intracellular organelles begin to change in function and appearance

apoptosis

The plasma membrane is maintained in —

• contents of cell packed into vesicles

necrosis

Plasma membrane is damaged in —

• cell explodes

phagocytosis

vesicles containing cell contents are eaten in —

enlarged

necrosis leads to — cell size

reduced

apoptosis leads to — cell size

intrinsic

cell tells itself to die

extrinsic

something outside the cell tells it to undergo apoptosis

monomers

inactive caspases exist as —

dimerization

the apoptotic signal brings 2 inactive caspase monomers together, causing —

cleave

initiator caspase monomers — each other to activate each other

protease

caspase is a —

• cleaves proteins

executioner caspases

initiator caspases cleave and activate —

amplification

Active initiator caspases can bump into and activate multiple copies of executioner caspase, resulting in —

Caspase 3

— activates CAD

CAD

caspase 3 activates —

caspase activated DNase

CAD

iCAD

— inhibits CAD

iCAD

executioner caspases degrade — to begin degradation of nuclear components

CAD

degrades DNA between histones to begin the orderly destruction of the nuclear components

activates

the cleavage of iCAD — CAD

limit infections

the immune system is very good at triggering apoptosis because it wants to —

• kills the cells that are harboring the virus

Fas ligand

The — on the lymphocyte binds to inactive Fas death receptor on infected cell

Fas death receptor

The Fas ligand on the lymphocyte binds to inactive — on infected cell

trimers

The Fas ligand and the Fas death receptor are —

FADD adaptor protein

Active Fas recruits — to the trimer

initiator caspase

FADD adaptor protein recruits —

caspase 8

initiator caspase for the extrinsic pathway

caspase 3 and 7

executioner caspases in extrinsic pathway

intrinsic

the pathway that relies exclusively on the mitochondria to control whether or not cells undergo apoptosis

mitochondria

also known as the executioners of the cell

cytochrome C

released from a leaky mitochondria

• binds to Apaf1 and dATP

Apaf1

Cytochrome C binds to —, causing a conformational change that exposes its CARD domain

apoptosome

the exposed CARD domain mediates the formation of the —

• made of 7 subunits

caspase 9

the active apoptosome recruits and activates 14 copies of — , and holds them in the correct position so they can cross cleave

pro-apoptotic, cytochrome C

Bak is —, permeabilizing the mitochondrial membrane to allow — to escape

Caspase Recruitment Domain

CARD

dATP

The conformational change in Apaf-1 allows it to bind —

oligomerization

Binding of dATP promotes the — of multiple Apaf-1 molecules (typically seven) into a wheel-like structure, forming the apoptosome

oligomerization

the process by which smaller units called monomers (single molecules) come together to form an oligomer, a complex made of a limited number of repeating units

caspase 9, CARD

The apoptosome recruits inactive — through interactions between the — domains of both proteins

free radicals

UV treatment creates — that react with and make mitochondrial membrane leaky

Bcl2 homology domains

BH

anti-apoptotic

Bcl family proteins like Bcl2, BclxL, and Mcl1 are —

• inhibit apoptosis by preventing mitochondrial outer membrane permeabilization (MOMP) and cytochrome c release

• Inhibit Bak and Bad (pro-apoptotic proteins)

pro-apoptotic

Bcl2 family effectors like Bak and Bax are —

• promote apoptosis by forming pores in the mitochondrial outer membrane, allowing the release of cytochrome c

pro-apoptotic

BH3 only proteins like Bad, Bim, Bid, Puma, and Noxa are —

Bak

activation of — causes it to aggregate in the mitochondrial membrane, forming pores that allow cytochrome c to escape (pro-apoptotic)

BclxL

— binds to Bak and inhibits it from aggregating and forming pores in the mitochondria

• anti-apoptotic

BH3

activated Bak contains a — domain, which allows it to bind to BclxL to become inhibited

BH3

The — domain binds to pro-apoptotic proteins, inhibiting their function

PH

The — domains of PDK1 and Akt bind to PIP3

Bad

Active Akt phosphorylates —

Bad

— inhibits apoptosis-inhibitory protein (Bcl2)

Bcl2, inhibition

When Akt phosphorylates Bad, Bad dissociates from —, which activates it

• this results in the — of apoptosis

BH3 domains

— enable pro-apoptotic proteins (e.g., Bax, Bak, Bid, and Bad) to bind to and neutralize anti-apoptotic Bcl-2 family members (e.g., Bcl-2, Bcl-xL, Mcl-1).

CARD

— domains help recruit initiator caspases (e.g., caspase-9) to the apoptosome

death domain

Fas death receptor contains an intracellular —

Death effector domain

The caspase 8 (initator caspase) interacts with the FADD adaptor protein using its —

death inducing signaling complex

DISC

DISC

Fas death receptor + FAD adaptor + caspases