Necroptosis, necrosis and secondary necrosis converge on similar cellular disintegration features.
Necroptosis, necrosis and secondary necrosis following apoptosis represent different modes of cell death that eventually result in similar cellular morphology including rounding of the cell, cytoplasmic swelling, rupture of the plasma membrane and spilling of the intracellular content. Subcellular events during tumor necrosis factor (TNF)-induced necroptosis, H(2)O(2)-induced necrosis and anti-Fas-induced secondary necrosis were studied using high-resolution time-lapse microscopy. The cellular disintegration phase of the three types of necrosis is characterized by an identical sequence of subcellular events, including oxidative burst, mitochondrial membrane hyperpolarization, lysosomal membrane permeabilization and plasma membrane permeabilization, although with different kinetics. H(2)O(2)-induced necrosis starts immediately by lysosomal permeabilization. In contrast, during TNF-mediated necroptosis and anti-Fas-induced secondary necrosis, this is a late event preceded by a defined signaling phase. TNF-induced necroptosis depends on receptor-interacting protein-1 kinase, mitochondrial complex I and cytosolic phospholipase A(2) activities, whereas H(2)O(2)-induced necrosis requires iron-dependent Fenton reactions.
Vanden Berghe
T
T
Department for Molecular Biomedical Research, VIB, Ghent, Belgium.
Vanlangenakker
N
N
Parthoens
E
E
Deckers
W
W
Devos
M
M
Festjens
N
N
Guerin
C J
CJ
Brunk
U T
UT
Declercq
W
W
Vandenabeele
P
P
D000818:Animals; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D042967:Electron Transport Complex I / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D007501:Iron / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D009336:Necrosis / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D054510:Phospholipases A2, Cytosolic / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity
D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D007501:Iron; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D054510:Phospholipases A2, Cytosolic; D042967:Electron Transport Complex I