A role for mitochondria in NLRP3 inflammasome activation.

Details

Serval ID
serval:BIB_72C82E06D655
Type
Article: article from journal or magazin.
Collection
Publications
Title
A role for mitochondria in NLRP3 inflammasome activation.
Journal
Nature
Author(s)
Zhou R., Yazdi A.S., Menu P., Tschopp J.
ISSN
1476-4687 (Electronic)
ISSN-L
0028-0836
Publication state
Published
Issued date
2011
Volume
469
Number
7329
Pages
221-225
Language
english
Abstract
An inflammatory response initiated by the NLRP3 inflammasome is triggered by a variety of situations of host 'danger', including infection and metabolic dysregulation. Previous studies suggested that NLRP3 inflammasome activity is negatively regulated by autophagy and positively regulated by reactive oxygen species (ROS) derived from an uncharacterized organelle. Here we show that mitophagy/autophagy blockade leads to the accumulation of damaged, ROS-generating mitochondria, and this in turn activates the NLRP3 inflammasome. Resting NLRP3 localizes to endoplasmic reticulum structures, whereas on inflammasome activation both NLRP3 and its adaptor ASC redistribute to the perinuclear space where they co-localize with endoplasmic reticulum and mitochondria organelle clusters. Notably, both ROS generation and inflammasome activation are suppressed when mitochondrial activity is dysregulated by inhibition of the voltage-dependent anion channel. This indicates that NLRP3 inflammasome senses mitochondrial dysfunction and may explain the frequent association of mitochondrial damage with inflammatory diseases.
Keywords
Animals, Autophagy/drug effects, Carrier Proteins/genetics, Carrier Proteins/metabolism, Cell Line, Cytoskeletal Proteins/genetics, Cytoskeletal Proteins/metabolism, Endoplasmic Reticulum/metabolism, Humans, Immunity, Innate, Inflammasomes/drug effects, Inflammasomes/metabolism, Inflammation/metabolism, Inflammation/pathology, Interleukin-1beta/metabolism, Interleukin-1beta/secretion, Macrophages/cytology, Macrophages/metabolism, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Mitochondria/drug effects, Mitochondria/metabolism, Reactive Oxygen Species/metabolism, Thioredoxins/genetics, Thioredoxins/metabolism, Voltage-Dependent Anion Channels/metabolism
Pubmed
Web of science
Create date
02/09/2011 10:00
Last modification date
03/03/2018 18:18
Usage data