Necrosis Flashcards
necrosis
morphological characteristics of gain in cell volume, swelling of organelles, plasma membrane rupture, subsequent loss of intracellular contents
necroptosis
type III PCD
morphological features of necrosis that is initiated by a programmed process involving “receptor-interacting protein kinase 1 and 3 aka RIP 1 and RIP 3
this process can be inhibited by necrostatin-1
what induces necrosis?
SOMETIMES:
- after death ligand
- after toll receptor ligand
- by viral infections and exposure to double stranded RNA
- high levels of ROS
- DNA damage
- massive insult to plasma membrane
- treatment with calcium ionophores
- uncoupling of respiration and oxidative phosphorylation
necrostatin-1
suppresses necrosis via death ligands
inhibits Receptor interacting protein kinase-1 RIP1
RIP 3 is the 2nd key component needed for necroptosis
found in cytosol, forms a complex with RIP1, inhibited by necrostatin-1, cleaved and inativated by caspase8
necrosome
a complex that mediates programmed necrosis
necrosome mechanism
- formation of a plasma membrane receptor complex that activates NF signaling pathway providing cIAP is present which causes ubiquitination of RIP1
- complex is released into the cytosol and FADD and pro0caspase-8 associate with the complex
- if no caspase 8 inhibitor is present then procaspase 8 is converted to caspase 8 and caspase 8 cleaves both RIP 1 and RIP 3 and the result is APOPTOSIS
- if an inhibitor of procaspase 8 activation or caspase 8 activity is present then the RIP1/RIP3 complex becomes the necrosome and activates processes that result in necrosis
macro-autophagy
type 2 programmed cell death
literally means to eat oneself
types of autophagy
microautophagy
macroautophagy
chaperone-mediated
induction of macroautophagy is mediated by
- nutrient deprivation
- energy depletion
- need to remove damaged proteins and organelles
- inhibiting normal suppressive signaling mechanism
mechanistic aspects of autophagosome synthesis
- receipt of autophagic signal
- inhibition of mTOR
- activation of ULK1 complex
- release of Beclin-1 and activation of VPS34
- formation of phagophore nucleus
- formation of Atg12-Atg5/atg16 complex
- encasement of cargo
- closure of phagophore to form autophagosome
- fusion of autophagosome with lysosomes
- degradation of autophagosome and its cargo
characteristics of cells undergoing autophagy
accumulation of cytosolic vacuoles with DOUBLE MEMBRANE
accumulation of LC3-II
accumulation of fluorescent puncta corresponding to either the aggregation of GFP-LC3 protein or staining with an antibody to LC3
pro-survival function of macro-autophagy
to prevent apoptosis or necrosis from occurring
involved in everyday maintenance of homeostasis
induced as a response to stress/injury
pro-death function of autophagy
cell death occurring in the absence of chromatin condensation, no caspase activation and accompanied by massive autophagic vacuolization of the cytoplasm
happens in very few cells
resistance
insensitivity to an agent due to an irreversible process that generally has a genetic/epigenetic basis
-can be innate or acquired
