SENP1-Sirt3 signaling promotes α-ketoglutarate production during M2 macrophage polarization.-猫眼课题宝

SENP1 - Sirt3信号通路在M2巨噬细胞极化过程中促进α - 酮戊二酸的产生。

DOI：

10.1016/j.celrep.2022.110660

发表时间：

2022-04

期刊：

Cell reports

影响因子：

8.8

通讯作者：

中科院分区：

生物学1区

文献类型：

作者：

Wei Zhou;Gaolei Hu;Jianli He;Tianshi Wang;Y. Zuo;Ying Cao;Quan Zheng;Jun Tu;Jiao Ma;R. Cai;Yalan Chen;Qiuju Fan;B. Dong;Hongsheng Tan;Qi Wang;Wei Xue;Jinke Cheng

代谢程序在巨噬细胞活化过程中改变，并影响巨噬细胞极化。谷氨酰胺分解促进α-酮戊二酸（αKG）蓄积，导致巨噬细胞M2极化期间含Jumonji结构域的蛋白D3（Jmjd 3）依赖性H3 K27 me 3去甲基化。然而，在巨噬细胞的M2极化过程中，αKG蓄积是如何调节的仍不清楚。这项研究表明，SENP 1-Sirt 3信号转导控制着α-氨基的分解，导致IL-4刺激的M2极化过程中αKG的蓄积。SENP 1-Sirt 3轴的激活通过αKG的积累经由β-氨基裂解增强M2巨噬细胞极化。我们还确定谷氨酸脱氢酶1（GLUD 1）作为线粒体中的乙酰化蛋白。SENP 1-Sirt 3轴使GLUD 1去乙酰化并增加其在β-氨基分解中的活性以促进αKG产生，从而导致巨噬细胞的M2极化。因此，SENP 1-Sirt 3信号转导通过β-氨基水解促进M2极化在αKG积累中起关键作用。

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.

SENP1-Sirt3 signaling promotes α-ketoglutarate production during M2 macrophage polarization.

SENP1 - Sirt3信号通路在M2巨噬细胞极化过程中促进α - 酮戊二酸的产生。

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