A study of "One-carbon metabolism supports S-Adenosylmethionine and histone methylation to drive inflammatory macrophages". Weiwei Yu, Zhen Wang, Kailian Zhang et al.
Description
Activated macrophages adapt their metabolic pathways to drive the pro-inflammatory phenotype, but less is known about the mechanistic basis for this process. Here we find that lipopolysaccharide (LPS) activates glycolysis offshoots pentose phosphate pathway (PPP), serine synthesis pathway (SSP), and one-carbon metabolism, whose synergism drives epigenetic reprogramming for the expression of interleukin-1β (IL-1β) but not tumor-necrosis factor-α in pro-inflammatory macrophages. In contrast to predominantly supporting nucleotide synthesis for rapidly dividing cells, one-carbon flux synergistically supported by glucose and serine metabolism integrate into methionine cycle through de novo ATP synthesis, and fuels the generation of S-adenosylmethionine (SAM) in pro-inflammatory macrophages. Impairments of these metabolic pathways or depletions of exogenous amino acids that feed SAM generation lead to anti-inflammatory outcomes, implicating SAM as a key immunometaboite during LPS-induced inflammation. Mechanistically, SAM generation and its controlled SAM/SAH ratio coordinately support histone H3 lysine 36 trimethylation (H3K36me3) to promote IL-1β production in response to LPS. We therefore identify a synergistic effect of glucose and amino acids metabolism on orchestrating SAM availability that is intimately link to the chromatin state for LPS-induced inflammation. The datasets mainly includes all the Western Blotting images used in the article. The ".jpg" files are named after figure identifier plus name of bloting protein, for example, "1A Actin.jpg" stands for the protein Actin of Figure 1A. The ".pptx" files consist of the labeled figure panel and some small descriptions. Every figure has a independent zip file, which involved all the ".jpg" and ".pptx" files associated with the corresponding figure in the article.