Glucose limitation activates AMPK coupled SENP1-Sirt3 signalling in mitochondria for T cell memory development.
Glucose limitation activates AMPK coupled SENP1-Sirt3 signalling in mitochondria for T cell memory development.
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葡萄糖限制激活线粒体中 AMPK 偶联的 SENP1-Sirt3 信号传导，促进 T 细胞记忆发育
DOI：
10.1038/s41467-021-24619-2
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发表时间：
2021-07-16
影响因子：
16.6
通讯作者：
Cheng J
中科院分区：
文献类型：
--
作者：
He J;Shangguan X;Zhou W;Cao Y;Zheng Q;Tu J;Hu G;Liang Z;Jiang C;Deng L;Wang S;Yang W;Zuo Y;Ma J;Cai R;Chen Y;Fan Q;Dong B;Xue W;Tan H;Qi Y;Gu J;Su B;Eugene Chin Y;Chen G;Wang Q;Wang T;Cheng J
代谢编程和线粒体动力学随T细胞分化影响T细胞命运和记忆发育；然而，如何控制T细胞记忆发育中的代谢重编程和线粒体动力学尚不清楚。在这里，我们提供的证据表明，SUMO蛋白酶SENP1通过Sirt3去ummoylation促进T细胞记忆的发展。SENP1-Sirt3信号增强Sirt3的去乙酰化酶活性，促进OXPHOS和线粒体融合。机制上，SENP1激活T细胞线粒体中Sirt3去乙酰化酶活性，导致线粒体金属蛋白酶YME1L1乙酰化降低。因此，YME1L1的去乙酰化抑制其对OPA1裂解的活性，从而促进线粒体融合，从而导致T细胞存活并促进T细胞记忆的发展。我们还发现糖酵解中间产物果糖-1,6-二磷酸（FBP）作为负调节因子抑制ampk介导的SENP1-Sirt3轴的激活并降低记忆发育。此外，葡萄糖限制会减少FBP的产生，并在T细胞记忆发育过程中激活AMPK。这些数据表明，葡萄糖限制激活AMPK和随后的SENP1-Sirt3信号传导，用于T细胞记忆发育。
Metabolic programming and mitochondrial dynamics along with T cell differentiation affect T cell fate and memory development; however, how to control metabolic reprogramming and mitochondrial dynamics in T cell memory development is unclear. Here, we provide evidence that the SUMO protease SENP1 promotes T cell memory development via Sirt3 deSUMOylation. SENP1-Sirt3 signalling augments the deacetylase activity of Sirt3, promoting both OXPHOS and mitochondrial fusion. Mechanistically, SENP1 activates Sirt3 deacetylase activity in T cell mitochondria, leading to reduction of the acetylation of mitochondrial metalloprotease YME1L1. Consequently, deacetylation of YME1L1 suppresses its activity on OPA1 cleavage to facilitate mitochondrial fusion, which results in T cell survival and promotes T cell memory development. We also show that the glycolytic intermediate fructose-1,6-bisphosphate (FBP) as a negative regulator suppresses AMPK-mediated activation of the SENP1-Sirt3 axis and reduces memory development. Moreover, glucose limitation reduces FBP production and activates AMPK during T cell memory development. These data show that glucose limitation activates AMPK and the subsequent SENP1-Sirt3 signalling for T cell memory development.
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影响因子：
56.9
作者：
Choudhary, Chunaram;Kumar, Chanchal;Mann, Matthias
通讯作者：
Mann, Matthias
SIRT3在饮食限制期间促进尿素周期和脂肪酸氧化。
影响因子：
16
作者：
Hallows WC;Yu W;Smith BC;Devries MK;Ellinger JJ;Someya S;Shortreed MR;Prolla T;Markley JL;Smith LM;Zhao S;Guan KL;Denu JM
通讯作者：
Denu JM
影响因子：
29
作者：
Civiletto G;Varanita T;Cerutti R;Gorletta T;Barbaro S;Marchet S;Lamperti C;Viscomi C;Scorrano L;Zeviani M
通讯作者：
Zeviani M
影响因子：
64.5
作者：
Chang CH;Curtis JD;Maggi LB Jr;Faubert B;Villarino AV;O'Sullivan D;Huang SC;van der Windt GJ;Blagih J;Qiu J;Weber JD;Pearce EJ;Jones RG;Pearce EL
通讯作者：
Pearce EL
影响因子：
7.3
作者：
Kurtulus S;Tripathi P;Hildeman DA
通讯作者：
Hildeman DA