| First Author | Shen L | Year | 2021 |
| Journal | Cell Metab | Volume | 33 |
| Issue | 5 | Pages | 971-987.e6 |
| PubMed ID | 33798471 | Mgi Jnum | J:309692 |
| Mgi Id | MGI:6707895 | Doi | 10.1016/j.cmet.2021.03.006 |
| Citation | Shen L, et al. (2021) Serine metabolism antagonizes antiviral innate immunity by preventing ATP6V0d2-mediated YAP lysosomal degradation. Cell Metab 33(5):971-987.e6 |
| abstractText | Serine metabolism promotes tumor oncogenesis and regulates immune cell functions, but whether it also contributes to antiviral innate immunity is unknown. Here, we demonstrate that virus-infected macrophages display decreased expression of serine synthesis pathway (SSP) enzymes. Suppressing the SSP key enzyme phosphoglycerate dehydrogenase (PHGDH) by genetic approaches or by treatment with the pharmaceutical inhibitor CBR-5884 and by exogenous serine restriction enhanced IFN-beta-mediated antiviral innate immunity in vitro and in vivo. Mechanistic experiments showed that virus infection or serine metabolism deficiency increased the expression of the V-ATPase subunit ATP6V0d2 by inhibiting S-adenosyl methionine-dependent H3K27me3 occupancy at the promoter. ATP6V0d2 promoted YAP lysosomal degradation to relieve YAP-mediated blockade of the TBK1-IRF3 axis and, thus, enhance IFN-beta production. These findings implicate critical functions of PHGDH and the key immunometabolite serine in blunting antiviral innate immunity and also suggest manipulation of serine metabolism as a therapeutic strategy against virus infection. |
