The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
4-Octyl itaconate inhibits aerobic glycolysis by targeting GAPDH to exert anti-inflammatory effects
Open accessAbstract
Activated macrophages switch from oxidative phosphorylation to aerobic glycolysis, similar to the Warburg effect, presenting a potential therapeutic target in inflammatory disease. The endogenous metabolite itaconate has been reported to regulate macrophage function, but its precise mechanism is not clear. Here, we show that 4-octyl itaconate (4-OI, a cell-permeable itaconate derivative) directly alkylates cysteine residue 22 on the glycolytic enzyme GAPDH and decreases its enzyme activity. Glycolytic flux analysis by U 13 C glucose tracing provides evidence that 4-OI blocks glycolytic flux at GAPDH. 4-OI thereby downregulates aerobic glycolysis in activated macrophages, which is required for its anti-inflammatory effects. The anti-inflammatory effects of 4-OI are replicated by heptelidic acid, 2-DG and reversed by increasing wild-type (but not C22A mutant) GAPDH expression. 4-OI protects against lipopolysaccharide-induced lethality in vivo and inhibits cytokine release. These findings show that 4-OI has anti-inflammatory effects by targeting GAPDH to decrease aerobic glycolysis in macrophages.
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Self-citationItaconate and itaconate derivatives target JAK1 to suppress alternative activation of macrophages
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Metadata
- Authors
- Liao, S.-T., Han, C., Xu, D.-Q., Fu, X.-W., Wang, J.-S., & Kong, L.-Y.
- Venue
- Nature Communications
- Published
- 2019-11-08
- Volume
- 10
- Issue
- 1
- Pages
- 5091-5091
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2988457676
- Cited by
- 451
- References
- 53
- FWCI
- 10.33
- Type
- journal article
- Language
- en
- Open access
- gold
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- Liao, S.-T., Han, C., Xu, D.-Q., Fu, X.-W., Wang, J.-S., & Kong, L.-Y. (2019). 4-Octyl itaconate inhibits aerobic glycolysis by targeting GAPDH to exert anti-inflammatory effects. Nature Communications. https://doi.org/10.1038/s41467-019-13078-5
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