Cell Death Flashcards
What is one of the main triggers for cell death?
DNA damage specifically DNA double stranded breaks
What makes cancer cells difficult to kill?
Lack of cell cycle control
Describe the morphological characteristics of necrosis
Cell membrane swelling and rupture
Cytoplasm: increased vacuolation, organelle degeneration and mito swelling
Nucleus: clumping and degradation of chromatin/DNA
Which cells are involved in necrosis and is inflammation present?
All cell types involved
Inflammation present
What are the biochemical features that lead to necrosis?
Extensive failure of normal physiological pathways that are essential for maintaining cellular homeostasis such as regulation of ion transport, energy production and pH balance
Describe some necrosis mechanisms
Two key players: RIP1 and PARP1
Ca2+ overload, mito uncoupling, increased O2 consumption, excessive ROS production, ATP depletion
NO caspases involved
Describe the morphological characteristics of apoptosis
Cell membrane: blebbing and fragmentation into apoptotic bodies
Cytoplasm: fragmentation and shrinkage
Nucleus: chromatin condensation and degradation -> nuclear fragmentation
Which cells are involved in apoptosis and is inflammation present?
Hematopoietic cells and their malignant counterparts (liquid tumors)
NO inflammation
Describe the biochemical features that may result in apoptosis
Cell membrane loses its asymmetry and phosphatidylserine becomes exposed on the cell surface
Caspases and mitochondria dependent
What are some apoptosis mechanisms?
DNA damage (ATM and p53) Death receptor signaling (TNF and Fas) Activation of sphingomyelinase Mito damage mediated by ceramide Bax and Bak
Describe the role Bax and Bak play in apoptosis
Though to induce permeabilization by forming pores upon oligomerization
Pro-apoptotic BH3 only family membranes can activate Bax/Bak by either binding to anti-apoptotic Bcl2 or the BH3 proteins can directly bind and activate Bax/Bak
What are the sensors and mediators of apoptosis?
Sensors: ATM, receptor, mitochondria
Mediators: p53, Bcl2, pro-apoptotic BH3 and Bax fam, cyt c, apoptotic protease activating factor 1 (APAF1)
What are the effectors of apoptosis?
Initiators: caspase 8, 9 and 10
Executioners: caspase 3, 6 and 7
Which members of the BH3 only family can activate Bax/Bak?
Bad, Bid, Bim, Puma and Noxa
What is autophagy?
A process responsible for degrading long lived proteins and cytoplasm organelles to maintain cellular homeostasis
Most a survival mechanism in response to several stresses (like DNA damage, protein aggregation, pathogens and nutrient starvation)
Describe the morphological characteristics of autophagy
Cell membrane: blebbing
Cytoplasm: accumulation of 2 autophagic vacuoles
Nucleus: partial chromatin condensation, no fragmentation
Which cell types are involved in autophagy and is inflammation present?
All cell types involved
No inflammation
Biochemical features of autophagy?
Caspase independent and increased lysosomal activity
What are the major players in autophagy?
Autophagy related genes (Atg)
Coiled-coil myosin like Bcl2 interacting protein (Beclin-1)(Atg-6) - initiation of the formation of the autophagosome (nucleation)
Microtubule associated protein 1A/B light chain 3 (LC3) - conjugation and elongation
What is mitotic catastrophe?
A type of cell death caused by aberrant mitosis and is associated with deficiencies in cell cycle checkpoints in mammals
Describe the morphological characteristics in mitotic catastrophe
No change in cell membrane Large cytoplasm (giant cell) Nucleus: micro and multinucleation, nuclear fragmentation
Which cells are involved in mitotic catastrophe and is inflammation present?
Most dividing cells involved
No inflammation
What are the biochemical features of mitotic activation?
Caspase independent (at early stage) and abnormal Cdk1/cyclin B activation
What are the mechanisms of mitotic catastrophe?
Defects in cell cycle checkpoints
Hyperamplification of centrosomes
Caspase 2 activation during metaphase
What is the fate of cells with aberrant mitosis?
Mitotic death (die without mitosis)
Delayed cell death
Senescence (exit mitosis and undergo permanent G1 arrest)
What is senescence?
Permanent cell cycle arrest and reproductive death
Can be replicative related to telomere shortening
Describe the morphological characteristics of senescence
No change in cell membrane
Cytoplasm: flat and granular
Nucleus: distinct heterochromatic structure
What cell types are involved in senescence and is inflammation present?
All cell types involved
Inflammation present but induced secretory factors from the senescent cell itself
What mechanism is used in senescence?
Same as DNA damage responses that activate cell cycle checkpoints (ex. ATM pathway)
Two pathways that lead to the same fate (growth arrest): p53-p21 and p16-Rb
