Cell Death Flashcards
Necrosis vs Apoptosis
Necrosis - involves a cellular response to injury that causes local inflammation and the bursting of the cell (pathological)
Apoptosis - cellular response to cellular stresses that cause the shrinkage of the cell to be taken up by phagocytes (physiological)
Six mechanisms of cell injury that would lead to cell death
ATP depletion, mitochondrial damage, accumulation of reactive oxygen species, influx of calcium, increased permeability of cellular membranes, accumulation of damaged DNA/misfolded proteins
Intrinsic pathway of apoptosis
DNA damaged, lack of O2 or other stress, increases mitochondrial permeability via Bcl2 effector activation. Cytochrome C is released to trigger activation of APAF-1 and initiator caspase 9. APAF-1 forms the apoptosome and pro-caspase 9 binds to this and autoactivates. Caspase 9 cleaves and activates caspase 3,6,7 (executioner caspases) and leads to cell death
Death receptors
Contain cytoplasmic death domain
Bcl family
Proteins that interact with the mitochondrial membrane and each other
Three types of Bcl-2 family proteins
Regulators, effectors, and sensors
Regulator Bcl-2 proteins
Bcl-2 or Bcl-X, maintain mitochondrial membrane permeability, anti-apoptotic
Effector Bcl-2 proteins
Bax or Bak, also known as BH123 proteins, form pores in the mitochondrial outer membrane, pro-apoptotic
Sensor Bcl-2 proteins
Bad, Bid, Bim, Puma, Noxa, also called BH3-only proteins, inhibit Bcl-2 and activate effectors, pro-apoptotic
Adaptors
APAF-1 (intrinsic) and FADD (extrinsic) both are pro-apoptotic
Caspases
Proteases that degrade cellular components
DNases
Digest genome
IAPs
Inhibitors of apoptosis
Anti-IAPs
Anti-inhibitors of apoptosis
Initiator caspases
Activate themselves and then activate effector or executioner caspases to start a signal cascade