Mitochondria: Sovereign of inflammation?
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TLDR
Mapping the connections between mitochondria, metabolism and inflammation is of great interest, as malfunctioning of this network is associated with many chronic inflammatory diseases.Abstract:
NLRP3 inflammasome-dependent inflammatory responses are triggered by a variety of signals of host danger, including infection, tissue damage and metabolic dysregulation. How these diverse activators cause inflammasome activation is poorly understood. Recent data suggest that the mitochondria integrate these distinct signals and relay this information to the NLRP3 inflammasome. Dysfunctional mitochondria generate ROS, which is required for inflammasome activation. On the contrary, the NLRP3 inflammasome is negatively regulated by autophagy, which is a catabolic process that removes damaged or otherwise dysfunctional organelles, including mitochondria. In addition to the processing and secretion of pro-inflammatory cytokines such as IL-1β, NLRP3 inflammasome activation also influences cellular metabolic pathways such as glycolysis and lipogenesis. Mapping the connections between mitochondria, metabolism and inflammation is of great interest, as malfunctioning of this network is associated with many chronic inflammatory diseases.read more
Citations
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Caspase Functions in Cell Death and Disease
TL;DR: Dysregulation of caspases underlies human diseases including cancer and inflammatory disorders, and major efforts to design better therapies for these diseases seek to understand how these enzymes work and how they can be controlled.
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Oxidized Mitochondrial DNA Activates the NLRP3 Inflammasome during Apoptosis
Kenichi Shimada,Timothy R. Crother,Justin Karlin,Jargalsaikhan Dagvadorj,Norika Chiba,Shuang Chen,V. Krishnan Ramanujan,Andrea J. Wolf,Laurent Vergnes,David M. Ojcius,Altan Rentsendorj,Mario Vargas,Candace R. Guerrero,Yinsheng Wang,Katherine A. Fitzgerald,David M. Underhill,Terrence Town,Moshe Arditi +17 more
TL;DR: The data reveal that oxidized mtDNA released during programmed cell death causes activation of the NLRP3 inflammasome, and provides a missing link between apoptosis and inflammaome activation, via binding of cytosolic oxidizedmtDNA to the NL RP3 infammasome.
Journal ArticleDOI
Reactive oxygen species: from health to disease.
TL;DR: ROS have crucial roles in normal physiological processes, such as through redox regulation of protein phosphorylation, ion channels, and transcription factors, and ROS are also required for biosynthetic processes, including thyroid hormone production and crosslinking of extracellular matrix.
Journal ArticleDOI
Reactive Oxygen Species in Health and Disease
Assim A. Alfadda,Reem M. Sallam +1 more
TL;DR: This review summarizes the key roles played by the ROS in both health and disease and provides brief perspective on some of the current research conducted in this area for better understanding of the ROS actions in various conditions of health and Disease.
Journal ArticleDOI
The inflammasome: an integrated view.
TL;DR: Investigation of how these and potentially other as yet uncharacterized signals are integrated by the NLRP3 inflammasome and the relevance of these biochemical events in vivo should provide new insight into the mechanisms of host defense and autoinflammatory conditions.
References
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Journal ArticleDOI
A role for mitochondria in NLRP3 inflammasome activation
TL;DR: It is shown that mitophagy/autophagy blockade leads to the accumulation of damaged, ROS-generating mitochondria, and this in turn activates the NLRP3 inflammasome, and may explain the frequent association of mitochondrial damage with inflammatory diseases.
Journal ArticleDOI
Cryopyrin activates the inflammasome in response to toxins and ATP
Sanjeev Mariathasan,David S. Weiss,Kim Newton,Jacqueline McBride,Karen O'Rourke,Meron Roose-Girma,Wyne P. Lee,Yvette Weinrauch,Denise M. Monack,Vishva M. Dixit +9 more
TL;DR: It is shown that cryopyrin-deficient macrophages cannot activate caspase-1 in response to Toll-like receptor agonists plus ATP, the latter activating the P2X7 receptor to decrease intracellular K+ levels.
Journal ArticleDOI
Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization
Veit Hornung,Franz Bauernfeind,Annett Halle,Eivind O. Samstad,Eivind O. Samstad,Hajime Kono,Kenneth L. Rock,Katherine A. Fitzgerald,Eicke Latz,Eicke Latz +9 more
TL;DR: It is demonstrated that silica and aluminum salt crystals activated inflammasomes formed by the cytoplasmic receptor NALP3, which senses lysosomal damage as an endogenous 'danger' signal.
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Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica.
Catherine Dostert,Virginie Pétrilli,Robin van Bruggen,Chad Steele,Brooke T. Mossman,Jürg Tschopp +5 more
TL;DR: It is shown that asbestos and silica are sensed by the Nalp3 inflammasome, whose subsequent activation leads to interleukin-1β secretion, and support its role as a major proinflammatory “danger” receptor in particulate matter–related pulmonary diseases.
Journal ArticleDOI
Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome
Kiichi Nakahira,Jeffrey A. Haspel,Jeffrey A. Haspel,Vijay A. K. Rathinam,Seon Jin Lee,Tamas Dolinay,Hilaire C. Lam,Joshua A. Englert,Marlene Rabinovitch,Manuela Cernadas,Hong Pyo Kim,Hong Pyo Kim,Katherine A. Fitzgerald,Stefan W. Ryter,Augustine M.K. Choi +14 more
TL;DR: This study suggests that autophagic proteins regulate NALP3-dependent inflammation by preserving mitochondria integrity and cytosolic translocation of mitochondrial DNA in response to lipopolysaccharide and ATP in macrophages.