Universität zu Köln

Ros, Uris, Pedrera, Lohans and Garcia-Saez, Ana J. (2020). Partners in Crime: The Interplay of Proteins and Membranes in Regulated Necrosis. Int. J. Mol. Sci., 21 (7). BASEL: MDPI. ISSN 1422-0067

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ros, Uris UNSPECIFIED UNSPECIFIED UNSPECIFIED Pedrera, Lohans UNSPECIFIED UNSPECIFIED UNSPECIFIED Garcia-Saez, Ana J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-338234
DOI:	10.3390/ijms21072412
Journal or Publication Title:	Int. J. Mol. Sci.
Volume:	21
Number:	7
Date:	2020
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	1422-0067
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DOMAIN-LIKE PROTEIN; CELL-DEATH; PORE FORMATION; FATTY-ACIDS; MLKL; NECROPTOSIS; FERROPTOSIS; PYROPTOSIS; ACTIVATION; TRANSLOCATION Multiple languages Biochemistry & Molecular Biology; Chemistry, Multidisciplinary Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/33823