Publication: Gasdermins mediate cellular release of mitochondrial DNA during pyroptosis and apoptosis
Authors
Torre-Minguela, Carlos de ; Gomez, Ana I. ; Couillin, Isabelle ; Pelegrín Vivancos, Pablo
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Publisher
Wiley
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DOI
https://doi.org/10.1096/fj.202100085R
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info:eu-repo/semantics/article
Description
© 2021 The Authors. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted Manuscript version of a Published Work that appeared in final form in The FASEB Journal. To access the final edited and published work see https://doi.org/10.1096/fj.202100085R
Abstract
Pyroptosis and intrinsic apoptosis are two forms of regulated cell death driven by active caspases
where plasma membrane permeabilization is induced by gasdermin pores. Caspase-1 induces
gasdermin D pore formation during pyroptosis whereas caspase-3 promotes gasdermin E pore
formation during apoptosis. These two types of cell death are accompanied by mitochondrial outer
membrane permeabilization due to BAK/BAX pore formation in the external membrane of
mitochondria, and to some extent this complex also affects the inner mitochondrial membrane
facilitating mitochondrial DNA relocalisation from the matrix to the cytosol. However, the detailed
mechanism responsible for this process has not been investigated. Herein, we reported that
gasdermin processing is required to induce mitochondrial DNA release from cells during pyroptosis
and apoptosis. Gasdermin targeted at the plasma membrane promotes a fast mitochondrial collapse
along with the initial accumulation of mitochondrial DNA in the cytosol and then facilitates the DNA’s
release from the cell when the plasma membrane ruptures. These findings demonstrate that
gasdermin action has a critical effect on the plasma membrane and facilitates the release of
mitochondrial DNA as a damage-associated molecular pattern.
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Citation
The FASEB Journal, 2021, Vol. 35, Issue 8 : e21757
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