Abstract
The past decades witnessed the discovery of novel modes of cell death, such as ferroptosis, pyroptosis and necroptosis, all of them presenting common necrotic traits. In this chapter, we revisit the early discoveries that unveiled necroptosis as a distinct cell death mechanism. We describe necroptosis, its main regulators and their role in maintaining cellular homeostasis and in the disease state. We conclude by discussing its phenotypic similarities with ferroptosis and the possible crosstalk between these pathways.
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Abbreviations
- 4HB:
-
N-terminal four-helix-bundle
- AML:
-
Acute myeloid leukemia
- ATP:
-
Adenosine triphosphate
- BSO:
-
buthionine sulfoximine
- CDC37:
-
Cell Division Cycle 37
- cFLIP:
-
CASP8 and FADD-like Apoptosis Regulator
- cIAPs:
-
Cellular Inhibitor of Apoptosis
- CLL:
-
Chronic lymphocytic leukemia
- CrmA:
-
Cytokine Response Modifier A
- CYLD:
-
Lysine 63 Deubiquitinase
- DAI:
-
DNA-dependent activator of IFN regulatory factors
- DAMPs:
-
Damage-Associated Molecular Patterns
- DR:
-
Death Receptor
- ESCRT-III:
-
Endosomal Sorting Complexes Required for Transport III
- FADD:
-
Fas-Associated Protein with Death Domain
- FasL:
-
Fas ligand
- FIN56:
-
Ferroptosis inducer 56
- FINO2:
-
Ferroptosis inducer endoperoxide
- GPX4:
-
Glutathione peroxidase 4
- GSH:
-
Glutathione
- HGMB-1:
-
High-Mobility Group Box 1 protein
- HSP90:
-
Heat-Shock Protein 90
- HSV:
-
Herpes Simplex virus
- IAV:
-
Influenza A virus
- ICP-6/10:
-
Infected cell protein 6/10
- IE1:
-
Immediate-Early gene product 1
- LUBAC:
-
Linear Ubiquitin Chain Assembly Complex
- M45/vIRA:
-
Viral inhibitor of RIP activation
- MAPK :
-
Mitogen-activated protein kinases
- MCMV:
-
murine cytomegalovirus
- MDA-5:
-
Melanoma differentiation-associated protein 5
- MLKL:
-
Mixed Lineage Kinase Domain Like Pseudokinase
- NADPH:
-
Nicotinamide adenine dinucleotide phosphate
- Nec-1:
-
Necrostatin-1
- NF-κB:
-
Nuclear factor kappa-light-chain-enhancer of activated B cells
- NS1:
-
Non-structural protein 1
- PI3K:
-
Phosphoinositide 3-kinases
- Ppm1b:
-
Phosphatase 1b
- PRR:
-
Pattern Recognition Receptors
- PTGS2:
-
Prostaglandin-endoperoxide synthase 2
- RHIM:
-
RIP Homology Motifs
- RIPK1:
-
Receptor-Interacting Serine/Threonine Protein Kinase 1
- RIPK3:
-
Receptor-Interacting Serine/Threonine Protein Kinase 3
- RSL3:
-
RAS-selective lethal
- TLR3/4:
-
Toll-like receptor-3/4
- TNF:
-
Tumour Necrosis Factor
- TNFR1:
-
Tumour Necrosis Factor Receptor 1
- TRADD:
-
TNFRSF1A-associated via death domain
- TRAF2/5:
-
TNF receptor associated factors 2/5
- TRAIL:
-
TNF-related apoptosis-inducing ligand
- TRPM:
-
Transient receptor potential melastatin
- VV :
-
Vaccinia virus
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Acknowledgements
This work was supported by Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP), Brazil, through the grants #2016/17628-0 and #2017/25009-1.
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Zanetti, L.C., Weinlich, R. (2021). Necroptosis, the Other Main Caspase-Independent Cell Death. In: Florez, A.F., Alborzinia, H. (eds) Ferroptosis: Mechanism and Diseases. Advances in Experimental Medicine and Biology, vol 1301. Springer, Cham. https://doi.org/10.1007/978-3-030-62026-4_7
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