2019
DOI: 10.1016/j.molcel.2019.06.039
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One-Carbon Metabolism Supports S-Adenosylmethionine and Histone Methylation to Drive Inflammatory Macrophages

Abstract: Highlights d LPS stimulates the PPP, SSP, and one-carbon metabolism d Glucose, serine, and methionine synergistically fuel SAM generation d Immunometabolite SAM promotes LPS-induced IL-1b production d SAM supports pro-inflammatory macrophages through H3K36me3

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Cited by 212 publications
(193 citation statements)
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“…To evaluate regulations of metabolic homeostasis in tobaccos responding to osmotic stress, the metabolite profiles of the tobacco leaves in the control and COR treatments under well-watered and PEG conditions were analyzed using an LC/MS platform by a professional laboratory (Applied Protein Technology, Shanghai, China) [34]. The PCA was performed for normal growth conditions and osmotic stress on both the control and the COR-treated tobacco seedlings (Figure 4).…”
Section: Metabolite Profilingmentioning
confidence: 99%
“…To evaluate regulations of metabolic homeostasis in tobaccos responding to osmotic stress, the metabolite profiles of the tobacco leaves in the control and COR treatments under well-watered and PEG conditions were analyzed using an LC/MS platform by a professional laboratory (Applied Protein Technology, Shanghai, China) [34]. The PCA was performed for normal growth conditions and osmotic stress on both the control and the COR-treated tobacco seedlings (Figure 4).…”
Section: Metabolite Profilingmentioning
confidence: 99%
“…Importantly, in addition to the previously known canonical NFκB and IRF3 signalling pathways (Clément et al, 2008), IKKε can engage in metabolic regulation by direct or indirect phosphorylation of key metabolic enzymes (PSAT1 and PDH, respectively) and these modifications can exert a downstream effect on gene expression, by engaging mitochondrial-nuclear ATF4-mediated signalling. While here we have shown that in breast 17 cancer cells IKKε-mediated changes in metabolism support proliferation, these metabolic alterations might also facilitate other cellular functions (Jones & Bianchi, 2015), for example, cytokine secretion in immune cells Tannahill et al, 2013;Rodriguez et al, 2019;Yu et al, 2019). Apart from providing novel mechanistic details of IKKε-mediated cellular metabolic changes, this work also indicates the necessity of further research to better understand the physiological and pathological role of IKKε in order to efficiently and selectively target tumour cells relying on this oncogene.…”
Section: Discussionmentioning
confidence: 66%
“…14 In myeloid cells, lipopolysaccharide stimulation enhanced serine one-carbon metabolism to support the production of interleukin-1b (IL-1b) in inflammatory macrophages. 15,16 Concordantly, inhibition of de novo serine synthesis protected mice from endotoxemia. 15 However, in a mouse model of Pasteurella multocida infection, exogenous administration of serine abated macrophage pro-inflammatory response, decreased bacterial colonization, and increased animal survival.…”
Section: One-carbon Metabolism and Sammentioning
confidence: 95%
“…18 It has been shown that the activity of methionine adenosyltransferase for SAM synthesis is essential for the function of T cells 19 and macrophages. 16 During methyl transfer, SAM is catalyzed by cytosolic or nuclear methyltransferases to form the methylated substrate and S-adenosylhomocysteine (SAH). SAH is hydrolyzed back to homocysteine and adenosine through a reversible reaction catalyzed by S-adenosylhomocysteine hydrolase to complete the methionine cycle ( Fig.…”
Section: One-carbon Metabolism and Sammentioning
confidence: 99%