Retta - L18
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What is the primary function of autophagy in cells?

  • To execute cell death directly
  • To increase protein aggregation within cells
  • To remove dysfunctional organelles and recycle their components (correct)
  • To inhibit the degradation of toxic components
  • What structure is formed when molecules engulfed by the autophagosome fuse with the lysosome?

  • Proteasome
  • Autophagolysosome (correct)
  • Mitochondrion
  • Cytoplasm
  • Which of the following is NOT a trigger for macroautophagy?

  • Hormones
  • Amino acids
  • DNA replication (correct)
  • Growth factors
  • Which protein complex is significantly involved in regulating autophagy through its activation?

    <p>mTORC 1</p> Signup and view all the answers

    What is the consequence of mTORC 1 activation in relation to autophagy?

    <p>It inhibits autophagy by phosphorylating target proteins.</p> Signup and view all the answers

    Which type of autophagy is primarily discussed in the context of the content?

    <p>Macroautophagy</p> Signup and view all the answers

    What is a critical aspect that should be considered regarding autophagy and cell death?

    <p>Autophagy is primarily a cell survival process.</p> Signup and view all the answers

    Which of the following describes the role of autophagy-related genes?

    <p>They are involved in regulating macroautophagy.</p> Signup and view all the answers

    What causes nrf2 to be induced at very high levels?

    <p>Accumulation of p62</p> Signup and view all the answers

    Which statement is true regarding reactive oxygen species (ROS)?

    <p>They are beneficial at physiological levels but can be harmful at high levels.</p> Signup and view all the answers

    How does autophagy relate to viral infections?

    <p>It is initially induced but may be inhibited by high viral loads.</p> Signup and view all the answers

    What role does Vitamin D play in cellular mechanisms?

    <p>It modulates autophagy and has antioxidant effects.</p> Signup and view all the answers

    What happens when apoptosis is disrupted during development?

    <p>It can cause developmental abnormalities.</p> Signup and view all the answers

    What is the primary function of autophagy in cells during stressful conditions?

    <p>To degrade abnormal proteins and organelles</p> Signup and view all the answers

    What dual role does autophagy play in cancer?

    <p>It can either protect or promote cancer cell survival.</p> Signup and view all the answers

    Which of the following is true about MTORC1 in relation to autophagy?

    <p>Inhibition of MTORC1 is required to induce autophagy</p> Signup and view all the answers

    What role does cytochrome c play in the intrinsic pathway of apoptosis?

    <p>It binds to apoptotic protease activating factor to induce caspase activation.</p> Signup and view all the answers

    What role does Rapamycin play in the context of autophagy?

    <p>It inhibits the activation of MTORC1</p> Signup and view all the answers

    What is a primary purpose of apoptosis in multicellular organisms?

    <p>To eliminate damaged or infected cells.</p> Signup and view all the answers

    Which of the following statements accurately describes the extrinsic pathway of apoptosis?

    <p>It primarily involves activation of initiator caspases via death receptor-ligand interaction.</p> Signup and view all the answers

    How do cells undergo programmed cell death?

    <p>Through apoptosis mechanisms.</p> Signup and view all the answers

    What is the function of the protein BID in apoptosis?

    <p>To connect intrinsic and extrinsic apoptotic pathways.</p> Signup and view all the answers

    What is the consequence of dysfunctional autophagy in cells?

    <p>Accumulation of dysfunctional organelles</p> Signup and view all the answers

    Which mechanism is primarily used to identify cells undergoing apoptosis in experimental studies?

    <p>Fluorescent dyes that mark apoptotic cells.</p> Signup and view all the answers

    Which substance is noted for being a biomarker for dysfunctional autophagy?

    <p>p62</p> Signup and view all the answers

    Which event can trigger the intrinsic pathway leading to apoptosis?

    <p>DNA damage occurring in the cell.</p> Signup and view all the answers

    How does starvation induce autophagy?

    <p>By inhibiting MTORC1</p> Signup and view all the answers

    What is the role of SMAC in the context of apoptosis?

    <p>To block XIAP, allowing caspase activation to proceed.</p> Signup and view all the answers

    What signifies a physiological role of nrf2 in cells?

    <p>Protecting cells from oxidative stress at normal levels.</p> Signup and view all the answers

    What type of diseases have been linked to dysfunctional autophagy?

    <p>Neurodegenerative and cardiovascular disorders</p> Signup and view all the answers

    What is the role of the NRF2 transcription factor in the context of autophagy?

    <p>It induces the transcription of antioxidant genes</p> Signup and view all the answers

    Which antioxidant compound is mentioned as potentially effective against CCM lesions?

    <p>Vitamin D</p> Signup and view all the answers

    What is the significance of reactive oxygen species in dysfunctional mitochondria?

    <p>They contribute to damage of macromolecules</p> Signup and view all the answers

    What role do ced3, ced4, and ced9 genes serve in C.elegans?

    <p>They play a key role in regulating apoptosis.</p> Signup and view all the answers

    Caspases are activated through a mechanism involving which of the following?

    <p>Proteolytic cleavage by other caspases.</p> Signup and view all the answers

    Which caspases are classified as cell death initiators?

    <p>Caspases 2 and 9.</p> Signup and view all the answers

    What is the primary function of bcl2 in relation to apoptosis?

    <p>It promotes cell survival.</p> Signup and view all the answers

    The primary targets of proteolytic enzymes activated by caspases include:

    <p>Cytosolic proteins and nuclear lamins.</p> Signup and view all the answers

    Why is the study of C.elegans significant in genetics research?

    <p>It allows mapping of cell lineage and apoptosis.</p> Signup and view all the answers

    Which of the following statements correctly describes the role of caspase activators?

    <p>They activate caspases to trigger apoptosis.</p> Signup and view all the answers

    What type of domain do initiator caspases typically contain?

    <p>Caspase activation and recruitment domain (CARD).</p> Signup and view all the answers

    Which statement about apoptotic pathways in vertebrates and C.elegans is true?

    <p>They reveal conserved molecular mechanisms.</p> Signup and view all the answers

    Study Notes

    Autophagy (Self-Eating)

    • Autophagy is a cellular process for removing dysfunctional organelles and protein aggregates.
    • Dysfunctional molecules are engulfed by autophagosomes, which fuse with lysosomes for degradation.
    • Resulting degradation products are recycled for cellular use, particularly to maintain cellular health.
    • Autophagolysomes facilitate the degradation of damaged organelles and proteins.
    • While autophagy is crucial for cell survival, its direct role in cell death is not concretely established.
    • Macroautophagy is the primary form of autophagy, activating complex processes in response to growth factors and fluctuating nutrient levels.

    Regulation of Autophagy

    • Autophagy is complexly regulated, influenced by stimuli like growth factors, amino acids, and hormones through PI3K signaling pathways.
    • Activation of the mTORC1 protein complex inhibits autophagy, while its inhibition stimulates the process.
    • Key inducers of autophagy include:
      • Starvation: Lack of nutrients triggers degradation of non-essential components to produce new nutrients.
      • Stressful conditions: Prompt autophagy to mitigate cellular distress through mTORC1 inhibition.
    • Rapamycin, derived from a bacterium, is effective in inducing autophagy by inhibiting mTORC1.

    Mitophagy

    • Mitophagy is a specific form of autophagy that targets and removes dysfunctional mitochondria, which can generate harmful reactive oxygen species (ROS).
    • Preventing the accumulation of dysfunctional mitochondria is essential for cellular health.

    Dysfunctional Autophagy and Diseases

    • Autophagy plays a critical role in various pathologies, including neurodegenerative and cardiovascular disorders.
    • Dysfunctional autophagy has been linked to diseases like cerebrovascular malformations (CCM) due to the accumulation of dysfunctional components.
    • Nobel Laureate Yoshinori Ohsumi highlighted the significance of dysfunctional autophagy in pathogenesis, particularly in the context of diseases like CCM.

    Therapeutic Approaches to Induce Autophagy

    • Targeting molecular pathways underlying disease mechanisms opens up therapeutic options.
    • Rapamycin is explored for its potential in treating CCM by inducing autophagy.
    • Antioxidants, including superoxide dismutases and vitamin D, play a protective role by alleviating oxidative stress and might help in disease prevention through autophagy induction.

    Autophagy Biomarkers and Mechanisms

    • P62 protein serves as a biomarker for dysfunctional autophagy; its accumulation indicates impaired processes.
    • Nrf2 is a major antioxidant transcription factor influenced by p62 levels, regulating genes that protect against oxidative stress.
    • There exists a balance with antioxidants; while beneficial, excessive levels can lead to harmful effects.

    Autophagy in Infections and Cancer

    • Viruses may inhibit autophagy to facilitate their replication within host cells, highlighting a dual nature in infection responses.
    • In cancer, autophagy can be both pro- and anti-tumorigenic, depending on the cellular context; it helps to either promote cancer cell survival or protect against DNA damage.

    Apoptosis

    • Apoptosis is a programmed mechanism crucial for normal development and tissue homeostasis, and eliminates damaged or potentially harmful cells.
    • Key functions include:
      • Morphogenetic roles such as interdigital cell death during limb development.
      • Sequential elimination of cells during metazoan development (ex: frog metamorphosis).

    Mechanisms Identifying Apoptosis

    • C. elegans has been instrumental in understanding apoptosis mechanisms due to its simplified cellular structure and known cell fates.
    • Important genes such as ced3, ced4, and ced9 have been identified as crucial regulators of apoptosis.
    • Ced9 and its vertebrate homolog Bcl-2 are implicated in cancer due to their roles in regulating apoptosis; Bcl-2's mutation can promote cancer cell survival.

    Caspase Activation in Apoptosis

    • Apoptosis is mediated by caspases, which are activated through proteolytic cascades.
    • Caspase activation is governed by various proteins, including Bcl-2 family members, which can promote or inhibit apoptosis.
    • Caspases are classified into initiation (like caspases 2, 8, and 10) and executioner caspases (caspases 3, 6, and 7), orchestrating the apoptotic response.

    Conclusion

    • Both autophagy and apoptosis are vital for maintaining cellular integrity and function.
    • They represent two interconnected processes where cells either self-eat dysfunctional components or self-kill damaged cells, balancing survival and homeostasis.### Apoptosis Overview
    • Apoptosis is a programmed cell death process triggered by extracellular or intracellular stimuli.
    • Distinct pathways exist: the extrinsic pathway (death receptors) and the intrinsic pathway (mitochondrial involvement).

    Initiator and Executor Caspases

    • Initiator caspases possess CARD or DAD domains facilitating interaction through adaptor proteins, promoting procaspase dimerization.
    • Reciprocal cleavage activates initiator caspases, leading to the activation of downstream executor caspases responsible for apoptosis.
    • Activated executor caspases target inhibitors of DNA endonucleases, crucial for DNA cleavage.

    Monitoring Apoptosis

    • Apoptosis can be monitored via gel electrophoresis or fluorescent protein labeling to identify apoptotic cells.

    Extrinsic Pathway

    • Triggered by extracellular signals binding to death receptors on plasma membranes, leading to apoptotic signaling.
    • Killer lymphocytes produce the ligand (e.g., Fas ligand) that activates death receptors, initiating the caspase cascade without provoking inflammation.

    Intrinsic Pathway

    • Activated by internal stressors such as protein misfolding, oxidative stress, reactive oxygen species (ROS), or DNA damage.
    • p53 protein plays a critical role, activating other proteins (like Puma and Fas) that promote mitochondrial changes leading to cytochrome c release.
    • Cytochrome c, upon release from mitochondria, associates with Apaf1 to facilitate the formation of aggregates that activate procaspase 9.

    Interconnection of Pathways

    • BID, a Bcl-2 family protein, links the extrinsic and intrinsic pathways; its cleavage by caspase 8 activates the intrinsic pathway.
    • Mitochondria release SMAC (an inhibitor of XIAP), preventing XIAP from inhibiting active caspase 9, which is essential for apoptosis to proceed.

    Key Factors and Mechanisms

    • Cytochrome c release directly triggers intrinsic apoptosis, while triggers such as ROS and DNA damage activate the process through p53.
    • Both pathways converge at executor caspases, ensuring effective execution of apoptosis.

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    Description

    This quiz explores the concepts of cell death, specifically focusing on apoptosis and autophagy. Understand how autophagy works in removing dysfunctional organelles and protein aggregations through the autophagosome-lysosome pathway. Test your knowledge on these critical cellular processes.

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