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

Alva M Casey, Michael P Murphy

Journal: Biochimica et biophysica acta. Molecular basis of disease 2022;1868(10):166481

PMID: 35792320

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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.

Address: MRC Mitochondrial Biology Unit, Biomedical Campus, University of Cambridge, Cambridge CB2 0XY, UK. Electronic address: [email protected].; MRC Mitochondrial Biology Unit, Biomedical Campus, University of Cambridge, Cambridge CB2 0XY, UK.

DOI: 10.1016/j.bbadis.2022.166481

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MeSH Terms: Lipopolysaccharides, Macrophages, Mitochondria, Superoxides, Toll-Like Receptor 4