| First Author | Yoo HJ | Year | 2022 |
| Journal | Cell Rep | Volume | 41 |
| Issue | 6 | Pages | 111598 |
| PubMed ID | 36351405 | Mgi Jnum | J:348610 |
| Mgi Id | MGI:7386594 | Doi | 10.1016/j.celrep.2022.111598 |
| Citation | Yoo HJ, et al. (2022) MsrB1-regulated GAPDH oxidation plays programmatic roles in shaping metabolic and inflammatory signatures during macrophage activation. Cell Rep 41(6):111598 |
| abstractText | Classically activated pro-inflammatory macrophages are generated from naive macrophages by pro-inflammatory cues that dynamically reprogram their fuel metabolism toward glycolysis. This increases their intracellular reactive oxygen species (ROS) levels, which then activate the transcription and release of pro-inflammatory mediators. Our study on mice that lack methionine sulfoxide reductase (Msr)-B1 shows that the resulting partial loss of protein methionine reduction in pro-inflammatory macrophages creates a unique metabolic signature characterized by altered fuel utilization, including glucose and pyruvate. This change also associates with hyper-inflammation that is at least partly due to sustained oxidation of an exposed methionine residue (M44) on glyceraldehyde 3-phosphate dehydrogenase (GAPDH), thereby inducing GAPDH aggregation, inflammasome activation, and subsequent increased interleukin (IL)-1beta secretion. Since MsrB1-knockout mice exhibit increased susceptibility to lipopolysaccharide (LPS)-induced sepsis, the MsrB1-GAPDH axis may be a key molecular mechanism by which protein redox homeostasis controls the metabolic profile of macrophages and thereby regulates their functions. |
