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Related Concept Videos

Necrosis01:16

Necrosis

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Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
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Overview of Cell Death01:30

Overview of Cell Death

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Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
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The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

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Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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The Extrinsic Apoptotic Pathway01:17

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The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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Caspases01:24

Caspases

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Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
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Autophagic Cell Death01:18

Autophagic Cell Death

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Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
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Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
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Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis

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An evolutionary perspective on the necroptotic pathway.

Yves Dondelinger1, Paco Hulpiau1, Yvan Saeys2

  • 1VIB Inflammation Research Center, Technologiepark 927, Zwijnaarde-Ghent, 9052, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, Zwijnaarde-Ghent, 9052, Belgium.

Trends in Cell Biology
|July 3, 2016
PubMed
Summary

Necroptosis, a key immune response, is surprisingly not universal across animals. Phylogenetic analysis shows its core components, except RIPK1, are poorly conserved, questioning necroptosis

Keywords:
DAIMLKLRHIMRIPK1RIPK3TRIF

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Area of Science:

  • * Evolutionary biology
  • * Immunology
  • * Cellular biology

Background:

  • * Innate immunity relies on receptors to detect and clear microbial invaders.
  • * Necroptosis, a form of programmed cell death, is a crucial component of the innate immune response, aiding in pathogen clearance and immune signaling.
  • * Key components of the necroptosis pathway, including TRIF, DAI, RIPK1, RIPK3, and MLKL, were presumed to be conserved across the animal kingdom due to their immune function.

Purpose of the Study:

  • * To investigate the evolutionary conservation of the necroptosis signaling axis throughout the animal kingdom.
  • * To determine if the core components of necroptosis are present across diverse animal species.
  • * To re-evaluate the universal role of necroptosis in innate immunity.

Main Methods:

  • * Phylogenetic analysis of necroptosis-associated genes (TRIF, DAI, RIPK1, RIPK3, MLKL).
  • * Comparative genomics across a wide range of animal species.
  • * Bioinformatic analysis of gene presence and conservation.

Main Results:

  • * Phylogenetic analysis revealed that the necroptosis signaling axis, with the exception of RIPK1, is poorly conserved across the animal kingdom.
  • * The majority of identified necroptosis components (TRIF, DAI, RIPK3, MLKL) show limited evolutionary conservation.
  • * This lack of conservation suggests potential alternative mechanisms for cell death and immune signaling in many species.

Conclusions:

  • * Necroptosis, as currently understood by its core components, is not a universally conserved immune mechanism in animals.
  • * The findings challenge the established role of necroptosis as a universal innate immune process.
  • * Further research is needed to explore alternative pathways that may mediate similar functions in species lacking canonical necroptosis components.