Lecture 11

Question 1

Apoptosis

Answer 1

• Highly regulated, reproducible cell death
• Necrosis accidental, uncontrolled cell death and can cause inflammation

Question 2

Caspase

Answer 2

• Synthesized as inactivate procaspases
• Signals initiate caspase cleavage to form caspase dimers
• Caspase cleave target proteins to trigger apoptosis
• Initiator caspase(8, 9) cleaved and activated in response to apoptotic signals -> cleave and activate executioner caspase(3, 6, 7) -> cleave target proteins to initiate apoptosis

Question 3

Alter cell surface lipid composition

Answer 3

• Healthy cells have specific lipid makeup -> use flippase
• Apoptotic cells maintain balance -> active scramblase

Question 4

Extrinsic pathway

Answer 4

• Caspase 8 has DED -> FADD adaptor protein has death domain and DED
• Fas death receptor at plasma membrane has death domain
• Killer lymphocytes express cell surface Fas ligands
• DISC assembly -> releaes domain and activate new caspase 8 -> activation of executioner caspase 3 and 7
• Healthy cells express decoy receptors without death domain -> no apoptosis

Question 5

Intrinsic pathway

Answer 5

• Cytochrome c binds to Apaf1 -> exposes CARD domain and oligomerization domain on Apaf1
• Apaf1 oligomerize -> unexposed CARD recruit caspase 9 monomers to form apoptosome and activation of caspase 9 -> activates executioner caspase
• Cyt c in mitochondrial intermembrane space: apoptotic stimuli trigger Bak and Bax to promote MOMP
• Bcl2 and BclxL bind to Bak and Bax to prevent formation of channels -> block MOMP -> anti-apoptotic
• Bad binds to Bcl2 and BclxL -> promote MOMP -> pro-apoptotic

Question 6

Inhibitor of Apoptosis

Answer 6

• IAP block apoptosis from accidentally occurring
• XIAP can directly block initiator and executioner caspases
• XIAP is anti-apoptotic
• Anti-IAP released whhen MOMP triggered -> inhibit XIAP -> pro-apoptotic