L41 - Apoptosis

overview

• cell necrosis is HARMFUL: injured cells rupture + damage neighbouring cells

• apoptosis is BENEFICIAL: cells no longer required or are a threat are dismantled → provide nutrients for other cells

• apoptosis is essential for multicellular organisms

Apoptosis Prep

→ most animal cells can do apoptosis, bc the cell already contains what is necessary, its just not active yet

contains:

1. procaspases (inactive monomers)

2. active Bcl2 protein protects the mitochondria

3. DNases are inactive (enzymes that break down DNA)

4. phosphatidylserines are hidden on the cytosol side of membrane

5. survival signals

• ALL cells need survival signals in addition to other signals - lack of these causes apoptosis

mech: survival signal → Bcl2 is made → mito. is protected

STEP 1: 3 Ways to Start Apoptosis

1. absence of survival signals → apoptosis

mech: no survival signal → Bcl2 ISNT made → CANT protect mito. → Cyt C is released from mito into cytosol → apoptosis

2. DNA damage → apoptosis

mech: severe DNA damage → p53 turns on PUMA gene → PUMA inhibits Bcl2 → Cyt C released into cytosol → apoptosis

3. WBCs attack infected cell → apoptosis

mech: T cell (WBC) uses its Fas ligand memb. proteins → bind to infected cells Fas receptors → apoptosis

• this uses contact dependent signalling

STEP 2: Activation of Procaspases

signals (Fas receptors, Cyt c) bring Procaspases (monomers) together → form an ACTIVE Caspases (dimer)

Caspases = protease, thus cuts things

• an active dimer

STEP 3: Cell destruction

1. caspases indirectly activate DNases → destroy chromosomes

• chopping up DNA : makes apoptosis irreversible + makes apoptotic bodies safe to eat (destroyed the virus/cancer genes)

• visualized using TUNEL technique = binds to DNA fragments

  • used since DAPI can only bind to intact DNA

example of this chromosome destruction: forming a mouse/human hand & forming a leaf

2. caspases directly destroy nuclear lamins → dismantle nuclear envelope

note: this ISNT the same as what occurs in prometaphase, bc thats inactivation of nuclear lamins, whereas caspases destroy nuclear lamins

3. cells round up & become apoptotic bodies

• caspases destroy cell-cell, cell-ECM, & cytoskeleton connections

STEP 4: Phagocytosis

→ apoptotic bodies are consumed by macrophages

mech : apoptotic bodies display PS phospholipids on ECM side of p. membrane → eat me signal

by: caspases activate scramblases & inactivate flippases (to stop them from keeping PS in the safe place)

Examinable Content

1. start

no survival signal → Bcl2 ISNT made → CANT protect mito. → Cyt C is released from mito into cytosol → apoptosis

or

severe DNA damage → p53 turns on PUMA gene → PUMA inhibits Bcl2 → Cyt C released into cytosol → apoptosis

or

T cell (WBC) uses its Fas ligand memb. proteins → bind to infected cells Fas receptors → apoptosis

2. signals (Fas receptors, Cyt c) bring Procaspases (monomers) together → form an ACTIVE Caspases (dimer)

3. caspases indirectly activate DNases → destroy chromosomes

4. caspases directly destroy nuclear lamins → dismantle nuclear envelope

5. caspases destroy cell-cell, cell-ECM, & cytoskeleton connections → form apoptotic bodies

6. apoptotic bodies display PS phospholipids on ECM side of p. membrane → eat me signal

• by: caspases activate scramblases & inactivate flippases (to stop them from keeping PS in the safe place)