Programmed Cell Death, Regeneration, Aging (2C) - Bio & Biochem
- Identify the hallmark DNA change in apoptosis detected by TUNEL assay.
- Internucleosomal DNA fragmentation producing many free -OH ends. Apoptotic endonucleases cleave DNA at internucleosomal sites, generating free -OH ends detectable by TUNEL assay for labeling fragmented DNA.
- Which caspases are initiator caspases in extrinsic and intrinsic pathways?
- Extrinsic: caspase-; intrinsic: caspase-. Initiator caspases activate downstream executioners; caspase- starts the extrinsic pathway via death receptors, while caspase- initiates the intrinsic via mitochondria.
- Which human tissue has high regenerative capacity due to abundant stem cells: liver or myocardium?
- Liver. The liver contains progenitor cells enabling extensive regeneration after injury, unlike the myocardium which primarily undergoes fibrotic repair.
- Identify the mitochondrial event that commits a cell to intrinsic apoptosis.
- Mitochondrial outer membrane permeabilization (MOMP) and cytochrome release. MOMP irreversibly commits the cell to apoptosis by releasing cytochrome , which activates the apoptosome and caspase cascade.
- Which Bcl- family proteins are anti-apoptotic and inhibit Bax/Bak?
- Bcl- and Bcl-xL. Anti-apoptotic Bcl- proteins sequester Bax/Bak, preventing mitochondrial permeabilization and thus inhibiting the intrinsic apoptotic pathway.
- Which pathway is suggested by cytochrome release with increased caspase- activity?
- Intrinsic (mitochondrial) apoptosis pathway. Cytochrome release from mitochondria activates caspase- via the apoptosome, hallmarking the intrinsic pathway response to internal stressors.
- What is autophagy, and what is its primary cellular purpose under nutrient stress?
- 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.
- What is necrosis, and what immediate membrane change typically occurs?
- 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.
- What is telomerase, and in which cell types is it typically highly active?
- 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.
- What is the extrinsic apoptosis pathway initiated by (ligand and receptor type)?
- Death ligands (e.g., FasL, TNF-) 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.
- Which caspases are the main executioner caspases in apoptosis?
- Caspase- and caspase-. Executioner caspases dismantle the cell by cleaving key proteins, leading to the morphological changes characteristic of apoptosis.
- What is the role of BH-only proteins in intrinsic apoptosis?
- They inhibit anti-apoptotic Bcl- proteins and activate Bax/Bak. BH-only proteins sense apoptotic stimuli and modulate Bcl- family balance by neutralizing inhibitors or directly activating effectors.
- Which plasma membrane change marks early apoptosis and enables phagocytosis?
- 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.
- Which signaling state promotes autophagy: high mTOR activity or low mTOR activity?
- Low mTOR activity promotes autophagy. mTOR inhibits autophagy when nutrients are abundant; low activity during starvation derepresses the pathway to promote cellular recycling.
- Identify the expected inflammatory outcome of apoptosis versus necrosis.
- 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.
- What are telomeres, and what happens to them with each somatic cell division?
- 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.
- What is the intrinsic apoptosis pathway primarily triggered by?
- 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.
- Which pathway is suggested by increased caspase- activity after Fas stimulation?
- Extrinsic (death receptor) apoptosis pathway. Fas stimulation activates death receptors, leading to caspase- initiation typical of the extrinsic pathway for immune-mediated apoptosis.
- What complex forms at death receptors to activate caspase-?
- DISC (death-inducing signaling complex) with FADD adaptor. DISC assembles at activated death receptors, facilitating caspase- activation through proximity-induced dimerization and autocleavage.
- What is the apoptosome, and which proteins assemble to form it?
- Apaf- + cytochrome + procaspase- complex. The apoptosome forms a wheel-like structure that activates caspase-, amplifying the apoptotic signal through initiator caspase function.
- Which Bcl- family members are pro-apoptotic effectors that form pores in mitochondria?
- Bax and Bak. Bax and Bak oligomerize to create mitochondrial pores, enabling release of apoptogenic factors in response to pro-apoptotic signals.
- What are caspases, and what amino acid do they cleave after?
- 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.