| First Author | Zhou W | Year | 2022 |
| Journal | Cell Rep | Volume | 39 |
| Issue | 2 | Pages | 110660 |
| PubMed ID | 35417703 | Mgi Jnum | J:326385 |
| Mgi Id | MGI:7283922 | Doi | 10.1016/j.celrep.2022.110660 |
| Citation | Zhou W, et al. (2022) SENP1-Sirt3 signaling promotes alpha-ketoglutarate production during M2 macrophage polarization. Cell Rep 39(2):110660 |
| abstractText | The metabolic program is altered during macrophage activation and influences macrophage polarization. Glutaminolysis promotes accumulation of alpha-ketoglutarate (alphaKG), leading to Jumonji domain-containing protein D3 (Jmjd3)-dependent demethylation at H3K27me3 during M2 polarization of macrophages. However, it remains unclear how alphaKG accumulation is regulated during M2 polarization of macrophages. This study shows that SENP1-Sirt3 signaling controls glutaminolysis, leading to alphaKG accumulation during IL-4-stimulated M2 polarization. Activation of the SENP1-Sirt3 axis augments M2 macrophage polarization through the accumulation of alphaKG via glutaminolysis. We also identify glutamate dehydrogenase 1 (GLUD1) as an acetylated protein in mitochondria. The SENP1-Sirt3 axis deacetylates GLUD1 and increases its activity in glutaminolysis to promote alphaKG production, leading to M2 polarization of macrophages. Therefore, SENP1-Sirt3 signaling plays a critical role in alphaKG accumulation via glutaminolysis to promote M2 polarization. |
