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Partners in Crime: The Interplay of Proteins and Membranes in Regulated Necrosis

Pyroptosis, necroptosis, and ferroptosis are well-characterized forms of regulated necrosis that have been associated with human diseases. During regulated necrosis, plasma membrane damage facilitates the movement of ions and molecules across the bilayer, which finally leads to cell lysis and releas...

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Autores principales: Ros, Uris, Pedrera, Lohans, Garcia-Saez, Ana J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177786/
https://www.ncbi.nlm.nih.gov/pubmed/32244433
http://dx.doi.org/10.3390/ijms21072412
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author Ros, Uris
Pedrera, Lohans
Garcia-Saez, Ana J.
author_facet Ros, Uris
Pedrera, Lohans
Garcia-Saez, Ana J.
author_sort Ros, Uris
collection PubMed
description Pyroptosis, necroptosis, and ferroptosis are well-characterized forms of regulated necrosis that have been associated with human diseases. During regulated necrosis, plasma membrane damage facilitates the movement of ions and molecules across the bilayer, which finally leads to cell lysis and release of intracellular content. Therefore, these types of cell death have an inflammatory phenotype. Each type of regulated necrosis is mediated by a defined machinery comprising protein and lipid molecules. Here, we discuss how the interaction and reshaping of these cellular components are essential and distinctive processes during pyroptosis, necroptosis, and ferroptosis. We point out that although the plasma membrane is the common target in regulated necrosis, different mechanisms of permeabilization have emerged depending on the cell death form. Pore formation by gasdermins (GSDMs) is a hallmark of pyroptosis, while mixed lineage kinase domain-like (MLKL) protein facilitates membrane permeabilization in necroptosis, and phospholipid peroxidation leads to membrane damage in ferroptosis. This diverse repertoire of mechanisms leading to membrane permeabilization contributes to define the specific inflammatory and immunological outcome of each type of regulated necrosis. Current efforts are focused on new therapies that target critical protein and lipid molecules on these pathways to fight human pathologies associated with inflammation.
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spelling pubmed-71777862020-04-28 Partners in Crime: The Interplay of Proteins and Membranes in Regulated Necrosis Ros, Uris Pedrera, Lohans Garcia-Saez, Ana J. Int J Mol Sci Review Pyroptosis, necroptosis, and ferroptosis are well-characterized forms of regulated necrosis that have been associated with human diseases. During regulated necrosis, plasma membrane damage facilitates the movement of ions and molecules across the bilayer, which finally leads to cell lysis and release of intracellular content. Therefore, these types of cell death have an inflammatory phenotype. Each type of regulated necrosis is mediated by a defined machinery comprising protein and lipid molecules. Here, we discuss how the interaction and reshaping of these cellular components are essential and distinctive processes during pyroptosis, necroptosis, and ferroptosis. We point out that although the plasma membrane is the common target in regulated necrosis, different mechanisms of permeabilization have emerged depending on the cell death form. Pore formation by gasdermins (GSDMs) is a hallmark of pyroptosis, while mixed lineage kinase domain-like (MLKL) protein facilitates membrane permeabilization in necroptosis, and phospholipid peroxidation leads to membrane damage in ferroptosis. This diverse repertoire of mechanisms leading to membrane permeabilization contributes to define the specific inflammatory and immunological outcome of each type of regulated necrosis. Current efforts are focused on new therapies that target critical protein and lipid molecules on these pathways to fight human pathologies associated with inflammation. MDPI 2020-03-31 /pmc/articles/PMC7177786/ /pubmed/32244433 http://dx.doi.org/10.3390/ijms21072412 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Ros, Uris
Pedrera, Lohans
Garcia-Saez, Ana J.
Partners in Crime: The Interplay of Proteins and Membranes in Regulated Necrosis
title Partners in Crime: The Interplay of Proteins and Membranes in Regulated Necrosis
title_full Partners in Crime: The Interplay of Proteins and Membranes in Regulated Necrosis
title_fullStr Partners in Crime: The Interplay of Proteins and Membranes in Regulated Necrosis
title_full_unstemmed Partners in Crime: The Interplay of Proteins and Membranes in Regulated Necrosis
title_short Partners in Crime: The Interplay of Proteins and Membranes in Regulated Necrosis
title_sort partners in crime: the interplay of proteins and membranes in regulated necrosis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177786/
https://www.ncbi.nlm.nih.gov/pubmed/32244433
http://dx.doi.org/10.3390/ijms21072412
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