Death of cells occurs mainly in two ways: Necrosis --(irreversible injury) changes produced by enzymatic digestion of dead cellular elements Apoptosis --vital process that helps eliminate unwanted cells--an internally programmed series of events effected by dedicated gene products
Difference between apoptosis and necrosis Necrosis Apoptosis Stimuli Hypoxia, Toxins Physiologic and pathologic conditions Histologic appearance Cell swelling, disruption of organelles Single cell, chromatin condensation, apoptotic bodies DNA breakdown Random and diffuse I nternucleosomal Mechanism ATP depletion membrane injury Gene activation, endonucleases , proteases Tissue reaction Inflammation No inflammation, phagocytosis of apoptotic bodies
What is Necroptosis?? Form of cell death Shares aspects of both necrosis and apoptosis Also known as Programmed necrosis Caspase independent programmed cell death
Characteristics Loss of ATP Cellular and organelle swelling Generation of Reactive oxygen species Release of lysosomal enzymes Rupture of plasma membrane Triggered by signal transduction pathways
Molecular mechanism
✅ It involves two kinases called receptor-interacting protein kinase 1 and 3 (RIPK1 and RIPK3). ✅ L igation of TNFR1 recruits these kinases into a multiprotein complex, and RIPK3 phosphorylates a cytoplasmic protein called MLKL.
✅ In response to its phosphorylation --> MLKL monomers assemble into oligomers T ranslocate from the cytosol to the plasma membrane --> plasma membrane disruption ✅ This explains the morphologic similarity of necroptosis with necrosis initiated by other injuries
Examples Physiologic--> Mammalian bone growth plate Pathologic--> Steatohepatitis, Acute pancreatitis, Parkinson disease, ischemic reperfusion injury Host defense against certain viruses like CMV.