All flashcards
Flashcard 1: Which caspases are the main executioner caspases in apoptosis?
Answer: Caspase-3 and caspase-7. Executioner caspases dismantle the cell by cleaving key proteins, leading to the morphological changes characteristic of apoptosis.
Flashcard 2: What is the role of BH3-only proteins in intrinsic apoptosis?
Answer: They inhibit anti-apoptotic Bcl-2 proteins and activate Bax/Bak. BH3-only proteins sense apoptotic stimuli and modulate Bcl-2 family balance by neutralizing inhibitors or directly activating effectors.
Flashcard 3: Identify the expected inflammatory outcome of apoptosis versus necrosis.
Answer: Apoptosis: minimal inflammation; necrosis: prominent inflammation. Apoptosis packages cellular contents into blebs for phagocytosis, avoiding inflammation, whereas necrosis causes content spillage that triggers immune response.
Flashcard 4: What is autophagy, and what is its primary cellular purpose under nutrient stress?
Answer: Lysosomal self-digestion; recycles macromolecules to maintain energy homeostasis. Autophagy degrades cytoplasmic components via lysosomes to recycle nutrients, serving as a survival mechanism during starvation or stress.
Flashcard 5: Which signaling state promotes autophagy: high mTOR activity or low mTOR activity?
Answer: Low mTOR activity promotes autophagy. mTOR inhibits autophagy when nutrients are abundant; low activity during starvation derepresses the pathway to promote cellular recycling.
Flashcard 6: Which human tissue has high regenerative capacity due to abundant stem cells: liver or myocardium?
Answer: Liver. The liver contains progenitor cells enabling extensive regeneration after injury, unlike the myocardium which primarily undergoes fibrotic repair.
Flashcard 7: What are telomeres, and what happens to them with each somatic cell division?
Answer: Chromosome end repeats; they shorten with each division in most somatic cells. Telomeres protect chromosome ends but erode due to incomplete replication by DNA polymerase, limiting somatic cell divisions and contributing to aging.
Flashcard 8: What is telomerase, and in which cell types is it typically highly active?
Answer: Reverse transcriptase extending telomeres; active in germ cells, stem cells, and cancers. Telomerase maintains telomere length to enable unlimited divisions in immortal cells like germ, stem, and cancer cells, countering replicative senescence.
Flashcard 9: Identify the hallmark DNA change in apoptosis detected by TUNEL assay.
Answer: Internucleosomal DNA fragmentation producing many free 3′-OH ends. Apoptotic endonucleases cleave DNA at internucleosomal sites, generating free 3′-OH ends detectable by TUNEL assay for labeling fragmented DNA.
Flashcard 10: Which plasma membrane change marks early apoptosis and enables phagocytosis?
Answer: Externalization of phosphatidylserine to the outer leaflet. Phosphatidylserine flips to the outer membrane in early apoptosis, serving as an 'eat me' signal for phagocytes to clear apoptotic cells without inflammation.
Flashcard 11: What are caspases, and what amino acid do they cleave after?
Answer: Cysteine-aspartate proteases; they cleave substrates after Asp residues. Caspases are proteolytic enzymes crucial for apoptosis, specifically targeting aspartate residues to dismantle cellular structures in a controlled manner.
Flashcard 12: Which caspases are initiator caspases in extrinsic and intrinsic pathways?
Answer: Extrinsic: caspase-8; intrinsic: caspase-9. Initiator caspases activate downstream executioners; caspase-8 starts the extrinsic pathway via death receptors, while caspase-9 initiates the intrinsic via mitochondria.
Flashcard 13: What is the extrinsic apoptosis pathway initiated by (ligand and receptor type)?
Answer: Death ligands (e.g., FasL, TNF-α) binding death receptors (Fas/TNFR). The extrinsic pathway is triggered by external signals where death ligands bind receptors, recruiting adaptors to activate caspases for apoptosis.
Flashcard 14: What complex forms at death receptors to activate caspase-8?
Answer: DISC (death-inducing signaling complex) with FADD adaptor. DISC assembles at activated death receptors, facilitating caspase-8 activation through proximity-induced dimerization and autocleavage.
Flashcard 15: What is the intrinsic apoptosis pathway primarily triggered by?
Answer: Internal stress such as DNA damage, growth factor withdrawal, or ER stress. The intrinsic pathway responds to intracellular damage signals, converging on mitochondrial permeabilization to release pro-apoptotic factors.
Flashcard 16: Identify the mitochondrial event that commits a cell to intrinsic apoptosis.
Answer: Mitochondrial outer membrane permeabilization (MOMP) and cytochrome c release. MOMP irreversibly commits the cell to apoptosis by releasing cytochrome c, which activates the apoptosome and caspase cascade.
Flashcard 17: What is the apoptosome, and which proteins assemble to form it?
Answer: Apaf-1 + cytochrome c + procaspase-9 complex. The apoptosome forms a wheel-like structure that activates caspase-9, amplifying the apoptotic signal through initiator caspase function.
Flashcard 18: What is necrosis, and what immediate membrane change typically occurs?
Answer: Uncontrolled cell death; early loss of membrane integrity and swelling. Necrosis results from severe injury leading to rapid membrane disruption and cellular swelling, causing inflammation due to leaked contents.
Flashcard 19: Which Bcl-2 family members are pro-apoptotic effectors that form pores in mitochondria?
Answer: Bax and Bak. Bax and Bak oligomerize to create mitochondrial pores, enabling release of apoptogenic factors in response to pro-apoptotic signals.
Flashcard 20: Which Bcl-2 family proteins are anti-apoptotic and inhibit Bax/Bak?
Answer: Bcl-2 and Bcl-xL. Anti-apoptotic Bcl-2 proteins sequester Bax/Bak, preventing mitochondrial permeabilization and thus inhibiting the intrinsic apoptotic pathway.
Flashcard 21: Which pathway is suggested by increased caspase-8 activity after Fas stimulation?
Answer: Extrinsic (death receptor) apoptosis pathway. Fas stimulation activates death receptors, leading to caspase-8 initiation typical of the extrinsic pathway for immune-mediated apoptosis.
Flashcard 22: Which pathway is suggested by cytochrome c release with increased caspase-9 activity?
Answer: Intrinsic (mitochondrial) apoptosis pathway. Cytochrome c release from mitochondria activates caspase-9 via the apoptosome, hallmarking the intrinsic pathway response to internal stressors.