SENP1-Sirt3 signaling promotes α-ketoglutarate production during M2 macrophage polarization.
Cell Rep
; 39(2): 110660, 2022 04 12.
Article
in En
| MEDLINE
| ID: mdl-35417703
ABSTRACT
The metabolic program is altered during macrophage activation and influences macrophage polarization. Glutaminolysis promotes accumulation of α-ketoglutarate (αKG), leading to Jumonji domain-containing protein D3 (Jmjd3)-dependent demethylation at H3K27me3 during M2 polarization of macrophages. However, it remains unclear how αKG accumulation is regulated during M2 polarization of macrophages. This study shows that SENP1-Sirt3 signaling controls glutaminolysis, leading to αKG accumulation during IL-4-stimulated M2 polarization. Activation of the SENP1-Sirt3 axis augments M2 macrophage polarization through the accumulation of αKG 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 αKG production, leading to M2 polarization of macrophages. Therefore, SENP1-Sirt3 signaling plays a critical role in αKG accumulation via glutaminolysis to promote M2 polarization.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sirtuin 3
/
Macrophage Activation
Language:
En
Journal:
Cell Rep
Year:
2022
Document type:
Article