Pro-inflammatory macrophages produce mitochondria-derived superoxide by reverse electron transport at complex I that regulates IL-1β release during NLRP3 inflammasome activation
University of Cambridge · MRC Mitochondrial Biology Unit · +6 more institutions
Abstract
Abstract Macrophages stimulated by lipopolysaccharide (LPS) generate mitochondria-derived reactive oxygen species (mtROS) that act as antimicrobial agents and redox signals; however, the mechanism of LPS-induced mitochondrial superoxide generation is unknown. Here we show that LPS-stimulated bone-marrow-derived macrophages produce superoxide by reverse electron transport (RET) at complex I of the electron transport chain. Using chemical biology and genetic approaches, we demonstrate that superoxide production is driven by LPS-induced metabolic reprogramming, which increases the proton motive force (∆p), primarily as elevated mitochondrial membrane potential (Δψ m ) and maintains a reduced CoQ pool. The key…
Citation impact
- FWCI
- 53.61
- Percentile
- 100%
- References
- 65
Authors
16- AMAlva M. CaseyCorresponding
University of Cambridge, MRC Mitochondrial Biology Unit
- DGDylan G. Ryan
University of Cambridge, MRC Mitochondrial Biology Unit
- HAHiran A. Prag
University of Cambridge
- SRSuvagata Roy Chowdhury
University of Cambridge, MRC Mitochondrial Biology Unit
- EMEloïse Marques
University of Cambridge, MRC Mitochondrial Biology Unit
Topics & keywords
- Superoxide
- Cell biology
- Reactive oxygen species
- Mitochondrion
- Chemistry
- Mitochondrial ROS
- Inflammasome
- Electron transport chain
- Responsible consumption and production