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Mitochondria released by cells undergoing TNF-α-induced necroptosis act as danger signals

Necrosis leads to the release of so-called damage-associated molecular patterns (DAMPs), which may provoke inflammatory responses. However, the release of organelles from dying cells, and the consequences thereof have not been documented before. We demonstrate here that mitochondria are released fro...

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Detalles Bibliográficos
Autores principales: Maeda, A, Fadeel, B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123071/
https://www.ncbi.nlm.nih.gov/pubmed/24991764
http://dx.doi.org/10.1038/cddis.2014.277
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author Maeda, A
Fadeel, B
author_facet Maeda, A
Fadeel, B
author_sort Maeda, A
collection PubMed
description Necrosis leads to the release of so-called damage-associated molecular patterns (DAMPs), which may provoke inflammatory responses. However, the release of organelles from dying cells, and the consequences thereof have not been documented before. We demonstrate here that mitochondria are released from cells undergoing tumor necrosis factor-α (TNF-α)-induced, receptor-interacting protein (RIP)1-dependent necroptosis, a form of programmed necrosis. The released, purified mitochondria were determined to be intact as they did not emit appreciable amounts of mitochondrial DNA (mtDNA). Pharmacological inhibition of dynamin-related protein 1 (Drp1) prevented mitochondrial fission in TNF-α-triggered cells, but this did not block necroptosis nor the concomitant release of mitochondria. Importantly, primary human macrophages and dendritic cells engulfed mitochondria from necroptotic cells leading to modulation of macrophage secretion of cytokines and induction of dendritic cell maturation. Our results show that intact mitochondria are released from necroptotic cells and suggest that these organelles act as bona fide danger signals.
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spelling pubmed-41230712014-08-15 Mitochondria released by cells undergoing TNF-α-induced necroptosis act as danger signals Maeda, A Fadeel, B Cell Death Dis Original Article Necrosis leads to the release of so-called damage-associated molecular patterns (DAMPs), which may provoke inflammatory responses. However, the release of organelles from dying cells, and the consequences thereof have not been documented before. We demonstrate here that mitochondria are released from cells undergoing tumor necrosis factor-α (TNF-α)-induced, receptor-interacting protein (RIP)1-dependent necroptosis, a form of programmed necrosis. The released, purified mitochondria were determined to be intact as they did not emit appreciable amounts of mitochondrial DNA (mtDNA). Pharmacological inhibition of dynamin-related protein 1 (Drp1) prevented mitochondrial fission in TNF-α-triggered cells, but this did not block necroptosis nor the concomitant release of mitochondria. Importantly, primary human macrophages and dendritic cells engulfed mitochondria from necroptotic cells leading to modulation of macrophage secretion of cytokines and induction of dendritic cell maturation. Our results show that intact mitochondria are released from necroptotic cells and suggest that these organelles act as bona fide danger signals. Nature Publishing Group 2014-07 2014-07-03 /pmc/articles/PMC4123071/ /pubmed/24991764 http://dx.doi.org/10.1038/cddis.2014.277 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Original Article
Maeda, A
Fadeel, B
Mitochondria released by cells undergoing TNF-α-induced necroptosis act as danger signals
title Mitochondria released by cells undergoing TNF-α-induced necroptosis act as danger signals
title_full Mitochondria released by cells undergoing TNF-α-induced necroptosis act as danger signals
title_fullStr Mitochondria released by cells undergoing TNF-α-induced necroptosis act as danger signals
title_full_unstemmed Mitochondria released by cells undergoing TNF-α-induced necroptosis act as danger signals
title_short Mitochondria released by cells undergoing TNF-α-induced necroptosis act as danger signals
title_sort mitochondria released by cells undergoing tnf-α-induced necroptosis act as danger signals
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123071/
https://www.ncbi.nlm.nih.gov/pubmed/24991764
http://dx.doi.org/10.1038/cddis.2014.277
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