8. Apoptosis & Autophagy Flashcards
Activation of PI3K causes…
Phosphorylation and inactivation of BH3-only proteins eg. Bad and Caspase 9
Autophagy
Degration of protein aggregates and organelles. Induced by starvation or stress.
Phases of autophagy: Initiation
Formation of a preautophagosomal membrane, leading to an isolation membrane (phagophore)
Phases of autophagy: Elongation
Phagophore elongates around target.
Phases autophagy: maturation
Creation of a autophagosome
Phases of autophagy: docking and fusion
Fusion of autophagosome with lyzosome.
Last phase of autophagy
Vesicle breakdown and degradation.
Beclin-1
Involved in initiation.
LC3
Involved in elongation.
mTOR and PI3K in autophagy
Prevents autophagy.
Three types of autophagy
Microautophagy, macroautophagy, chaperone-mediated autophagy.
Selective autophagy
Cargo are recognized through specific receptor proteins and targeting to autophagocytic proteins as Atg10 LC3.
Results of autophagy
Can result in cell survival of starved cells. Alternatively cell death.
Inducers of autophagy
Starvation, GF-deprivation, oxygen shortage, IR, chemotherapy.
Autophagy and apoptosis regulatory relationship.
Mutally inhibitory but can share upstream activator.
Ways for autophagic cytoprotection
Restoring metabolic homeostasis, removal of protein aggregates and harmful organelles.
Ways for autphagy-mediated cell deaths
Self-destruction, cellular atrophy.
Hallmarks of autophaic cell death.
Membrane blebbing, no DNA damage, increased number if autophagic vesicles, caspase independent.
LC3 puncta
Indicative of autophagic initiation
Beclin-1 regulation
Regulated by Bcl-2 proteins by binding and sequestering Beclin-1 throigh Beclin-1 BH3. BH3-only proteins can bind and sequester Bcl-2 and induce autophagy.
Autophagic tumor supression
Autophagy can be an adaptation to limited nutrients in tumors but can be detrimental to tumor cells.
Tumor initiation vs. progression
Autophagy can limit tumor initiation by clearing damaged proteins and organelles. In contrast it can also promote further tumor growth.