10 Questions
What is the role of active caspase 9 in apoptosis?
To initiate the caspase proteolytic cascade
What is the function of the death domain (DD) in TNFR?
To interact with the death receptors to transmit the apoptotic signal
What is the role of FADD in apoptosis?
To contain the death domain to interact with death receptors
What is the result of the interaction between FasL and the Fas death receptor?
Initiation of apoptotic cell death
What is the function of caspases in apoptosis?
To degrade cellular components in the apoptotic cell
What is the mechanism of caspase activation?
Through the post-translational modification of the proenzyme
What is the role of T-cytotoxic cells in apoptosis?
To express Fasl to interact with the Fas death receptor
What is the difference between Fas and TNFR1 in apoptosis?
Fas has strong death-inducing capability, while TNFR1 has weak death-inducing capability
What is the function of the adaptor molecules FADD and TRADD?
To interact with death receptors to transmit the apoptotic signal
What is the role of the tumor necrosis factor receptor (TNFR) in apoptosis?
To recognize specific ligands to transmit the apoptotic signal
Study Notes
Cell Death
- All cells eventually die by either necrosis or apoptosis.
Necrosis
- Passive, pathological process
- Induced by cellular injury or accidental means
- Often involves the simultaneous death of groups of cells
- Necrotic cells have ruptured cell membranes, causing cytoplasm and organelles to spill into surrounding tissue fluids
- Often induces an inflammatory response
Apoptosis
- Active, normal, physiological process
- Removes individual cells without damaging neighboring cells or inducing inflammation
- Cells have a characteristic "blebbed" appearance of their membranes
- Fundamental to cellular and tissue physiology, akin to cell division and differentiation
- Disturbances in apoptosis pathways may lead to cancers, autoimmune diseases, and neurodegenerative disorders
Characteristics of Apoptosis
- Cell shrinkage, but not lysis
- Plasma membrane remains intact, but portions bud off (blebbing)
- Phosphatidylserine in the inner membrane flips to the cell surface, serving as an "eat-me" signal to phagocytic cells
- Mitochondria releases cytochrome c in an ATP-dependent process, but remains within blebs
- Chromatin segments and condenses
Biological Significance of Apoptosis
- Removal of damaged cells
- Removes cells damaged beyond repair, infected, or starved, saving nutrition and preventing viral spread
- p53 protein halts cell cycle and stimulates apoptosis
- During development, apoptosis removes excess cells for normal development and function
- Selective apoptosis "sculpts" the developing tissues
- Incomplete apoptosis can result in abnormal structures
Initiation of Apoptosis
- Apoptosome (Internal Cell Death Program)
- Initiated by irreparable damage to cellular components or DNA
- Bax (proapoptotic protein) is inserted into the mitochondrial membrane, allowing cytochrome c to exit into the cytoplasm
- Cytochrome c in the cytosol triggers the formation of Apoptosome using ATP
- Cytoplasmic cytochrome c activates the apoptotic protease activating factor (Apaf-1) adaptor protein, which activates caspase 9
- Death receptor (External Cell Death Program)
- Triggered by death receptors (e.g., Fas, TNFR)
- Recognizes specific ligands, such as TNFR and Fas ligand
- Adaptor molecules (e.g., FADD, TRADD) interact with death receptors to transmit the apoptotic signal to the death machinery
Caspase Family of Proteases
- Stimulated to degrade cellular components in the apoptotic cell
- Proteases that are major effectors of apoptotic cell death
- Members of the cysteine protease class
- Synthesized as inactive zymogen or proenzyme forms and are activated to become functional proteases when needed
This quiz covers the basics of cell death, including necrosis and apoptosis. Learn about the differences between these two processes and how they affect cells and tissues.
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