scholarly journals Mitochondrial Reactive Oxygen Species Induces NLRP3-Dependent Lysosomal Damage and Inflammasome Activation

2013 ◽  
Vol 191 (10) ◽  
pp. 5230-5238 ◽  
Author(s):  
Michelle E. Heid ◽  
Peter A. Keyel ◽  
Christelle Kamga ◽  
Sruti Shiva ◽  
Simon C. Watkins ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Inflammasome Activation ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species

scholarly journals Macrophages utilize mitochondrial fission to enhance mROS production during responses to Streptococcus pneumoniae

2019 ◽  
Author(s):  
Mohammed Mohasin ◽  
Katharin Balbirnie-Cumming ◽  
Emily Fisk ◽  
Elizabeth C. Prestwich ◽  
Clark D. Russell ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Streptococcus Pneumoniae ◽  
Oxidative Phosphorylation ◽  
Reactive Oxygen ◽  
Inflammasome Activation ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Mitochondrial Fragmentation ◽  
Bacterial Killing ◽  
Form Complex

AbstractImmunometabolism and regulation of mitochondrial reactive oxygen species (mROS) control the immune effector phenotype of differentiated macrophages. Mitochondrial function requires dynamic fission and fusion, but whether effector function is coupled to altered dynamics during bacterial responses is unknown. We show that macrophage mitochondria undergo fission after 12 h of progressive ingestion of live Streptococcus pneumoniae (pneumococci), without evidence of Drp-1 phosphorylation at S616. Fission is associated with progressive reduction in oxidative phosphorylation but increased mROS generation. Fission is enhanced by mROS production, PI3Kγ signaling and by cathepsin B, but is independent of inflammasome activation or IL-1β generation. Inhibition of fission reduces bacterial killing. Fission is associated with Parkin recruitment to mitochondria, but not mitophagy. Fission occurs upstream of apoptosis induction and independently of caspase activation. During macrophage innate responses to bacteria mitochondria shift from oxidative phosphorylation and ATP generation to mROS production for microbicidal responses by undergoing fission.Author summaryChanges in metabolism regulate function in immune cells, including macrophages which are key cells in pathogen clearance. Mitochondria are cellular organelles that generate energy during metabolism but also mitochondrial reactive oxygen species (mROS) that contribute to bacterial killing. Mitochondria are dynamic organelles that form complex networks with varying degrees of fragmentation or fusion, but the functional consequences of these processes on macrophage function during bacterial infection are unknown. We show that sustained ingestion of live bacteria triggers mitochondrial fragmentation, reducing metabolism but enhancing mROS generation. Mitochondrial fragmentation is not part of a clearance pathway for damaged mitochondria and is initiated before signs of cell death. Macrophage signalling pathways activated during infection, and mROS generation, enhance mitochondrial fragmentation, and inhibition of pathways promoting fragmentation reduces bacterial killing. Overall, these findings suggest that responses to ingested bacteria trigger mitochondrial fragmentation, allowing mitochondria to switch from energy generation during metabolism to organelles facilitating bacterial killing.

scholarly journals Attenuating Effect of Chlorella Extract on NLRP3 Inflammasome Activation by Mitochondrial Reactive Oxygen Species

2021 ◽  
Vol 8 ◽  
Author(s):  
Yuya Nakashima ◽  
Kazuhito Gotoh ◽  
Soichi Mizuguchi ◽  
Daiki Setoyama ◽  
Yurie Takata ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Nlrp3 Inflammasome ◽  
Reactive Oxygen ◽  
Food Supplement ◽  
Inflammasome Activation ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Nlrp3 Inflammasome Activation

The NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) inflammasome has been linked to the pathogenesis of a wide variety of human diseases. Although many drugs and inhibitors have been developed to treat NLRP3-associated diseases, only limited clinical data support their efficacy and safety. Chlorella, a unicellular green alga that is widely and safely used as a food supplement, contains various antioxidants. In this study, we obtained a fat-soluble extract from Chlorella (CE) and demonstrated that it reduced NLRP3 inflammasome activation by inhibiting mitochondrial reactive oxygen species and caspase-1 activation. In addition, CE supplementation attenuated lipopolysaccharide-induced interleukin 1β transcription through activation of hypoxia-inducible factor 1α in vitro and in vivo. As Chlorella is a safe and useful food supplement, it may be a practical pharmacological approach for treating NLRP3-driven diseases.

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