Apoptosis

Act I – The Ides Approach (Signal Received)#### Flashcard 1 (Act 1, Scene 2):Quote: “Beware the Ides of March.”

Apoptosis begins with a signal, sensed by either:1. Extrinsic pathway: death ligands (e.g., FasL, TNF-α) bind death receptors (e.g., Fas, TNFR1).2. Intrinsic pathway: internal stress (DNA damage, ROS, ER stress) triggers mitochondrial alarm.The cell is warned — and begins to prepare for a controlled downfall.

Act II – The Senate Conspires (Initiation Complex Forms)#### Flashcard 2 (Act 2, Scene 1):Quote: “It must be by his death… And for my part, I know no personal cause to spurn at him, but for the general.”

1. Extrinsic Pathway: Death receptor + ligand recruit FADD (Fas-associated death domain). FADD binds pro-caspase-8, forming DISC (Death-Inducing Signaling Complex).2. Intrinsic Pathway: Mitochondria release cytochrome c → binds Apaf-1 → recruits pro-caspase-9 → forms apoptosome.The machinery is in place. The knives are drawn.

Act III – Et Tu, Caspase? (Initiator Caspases Strike)#### Flashcard 3 (Act 3, Scene 1):Quote: “Et tu, Brute? Then fall, Caesar!”

Caspase-8 (extrinsic) or caspase-9 (intrinsic) becomes activated in the DISC or apoptosome. They cleave and activate executioner caspases:1. Caspase-32. Caspase-63. Caspase-7The process becomes irreversible. Caesar — or the cell — cannot be saved.

Act IV – Rome Falls in Order (Execution Phase)#### Flashcard 4 (Act 4, Scene 2):Quote: “O Julius Caesar, thou art mighty yet! Thy spirit walks abroad and turns our swords in our own proper entrails.”

Executioner caspases cleave dozens of substrates:1. PARP (DNA repair)2. lamins (nuclear envelope)3. cytoskeletal proteinsThe cell undergoes:1. Chromatin condensation2. DNA fragmentation3. Membrane blebbing4. Formation of apoptotic bodiesAll without inflammation — no HMGB1, no IL-1β. Rome falls gracefully.