Uncovering the source of mitochondrial superoxide in pro-inflammatory macrophages: Insights from immunometabolism

Biochim Biophys Acta Mol Basis Dis. 2022 Oct 1;1868(10):166481. doi: 10.1016/j.bbadis.2022.166481. Epub 2022 Jul 2.

Abstract

Mitochondrial-derived reactive oxygen species are important as antimicrobial agents and redox signals in pro-inflammatory macrophages. Macrophages produce superoxide in response to the TLR4 ligand LPS. However, the mechanism of LPS-induced superoxide generation is not fully understood. Superoxide is produced at complex I and complex III of the electron transport chain. Production of superoxide at either of these sites is highly dependent on the metabolic state of the cell which is dramatically altered by TLR4-induced metabolic reprogramming. This review will outline how metabolism impacts superoxide production in LPS-activated macrophages downstream of TLR4 signalling and address outstanding questions in this field.

Keywords: Complex I; Macrophages; Metabolism; Mitochondria; Reverse electron transport; Superoxide.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Lipopolysaccharides / metabolism
  • Lipopolysaccharides / pharmacology
  • Macrophages / metabolism
  • Mitochondria / metabolism
  • Superoxides* / metabolism
  • Toll-Like Receptor 4* / metabolism

Substances

  • Lipopolysaccharides
  • Toll-Like Receptor 4
  • Superoxides