Cell Death: Apoptosis, Necrosis and Autophagy Flashcards
Summarize the Steps of the Intrinsic Apoptotic pathway.
DNA damage > p53 activated (if no cell repair then) > PUMA and NOXA > bind and block BCL-2 activity > Bax/BAK > Cytochrome C released > APAF1 > APOPTOSOME > Procaspace 9 cleaved > Initiator Caspase 9 > Effector caspaces 3,6 and 7 boost into effect > Apoptosis!
Summarize the Steps of the Apoptotic Extrinsic Pathway.
APO/TRAIL ligand binds > DR4/5 receptors > DISC assembled rapidly > FADD recruited > recruit Caspaces 8,10 > activates BID > binds BCL-2 to indirectly activate Bax/BAK or directly bind it to activate it > Apoptosis!
*Can be expressed on VIRUS-INFECTED CELLS
At what 2 steps (molecules) do the intrinsic and extrinsic pathway converge?
- BID complex and…
2. Effector Caspaces 3,6 and 7
Define Autophagy.
What happens, organelles involved, inflammation?
Induction > autophagosome formation > autophagosome-lysosome fusion > autophagosome breakdown. SELF-CANNIBALISM *can be necessary
Ex: mitochondria enclosed in AUTOPHAGOSOMES to be degraded by lysosome for cellular material
Moderate inflammation
Define Necrosis.
What happens, Noticeable features, Inflammation?
Irreversible cell damage caused by toxins or infection.
Features: swelling, cell-rupture, clumping (like many bubbles of PM) and degradation of nuclear DNA; MANY ABNORMAL GRANULES
SEVERE inflammation
Define Apoptosis.
What happens, features, inflammation?
Self-destruction of cells with irreparable infection or DNA damage caused by activation of mitochondrial (apoptotic) enzymes.
Features: cell shrinkage, chromatin condensation (LARGE ROUND NUCLEUS), BLEBBING
NO inflammation
How does autophagy relate to the mTOR pathway?
Autophagy is induced by the inactivated mTOR serine-threonine kinase. MTOR, when ON,usually inhibits autophagy in nutrient rich conditions. However, in starvation conditions, mTOR is inactivated, enabling txn of autophagy-genes.
What are the key cytoplasmic and biochemical features of necrosis?
Increased vacuolation, organelles degradation.
Loss of regulation for ion homeostasis.
What is the death receptor that triggers Extrinsic-Apoptosis pathway?
What cytoplasmic molecule is part of the DISC complex after the ligands bind DR4/5?
Fas Receptor;
FADD
The BH multi domain protein ______ functions against apoptosis to promote cell survival.
BCL-2
*Anti-apoptotic
The mitochondrial based _______ protein in the intermembrane space close to the outer membrane binds with counterpart ______ in the cytosol to puncture the mitochondria. This allows the molecule, __________ to be released.
BAK
BAX
Cytochrome C
The BH3 class of proteins pro-apoptotic such as _______ and _______ bind BCL-2 to reduce its expression. Therefore it allows more free ________ and _______ to be free and start apoptosis.
NOXA and PUMA
BAX and BAK
*Apoptotic
There are a few cells in a tissue sample that are blebbing, and indicate cell shrinkage as well as chromatin condensation. As a key feature, there is no __________. This cell is undergoing ________.
No inflammation
Apoptosis
A cell is observed under LM with sequestered mitochondria fused in a vesicle in close proximity to a lysosome. This cell is undergoing _________ and the vesicle is called an __________. Is there inflammation?
Autophagy
Autophagosome
Moderate inflammation
A large sample of muscle cells collected from a septic patient is observed under a LM with cellular contents spewed out. The _________ is degrading in clumps and there are many more vacuoles than expected in this cell type. This tissue sample is undergoing _______. Is there inflammation?
Nuclear DNA
Necrosis
SEVERE inflammation
