Toll-like receptor 9 protects non-immune cells from stress by modulating mitochondrial ATP synthesis through the inhibition of SERCA2.
Toll-like receptor 9 protects non-immune cells from stress by modulating mitochondrial ATP synthesis through the inhibition of SERCA2.
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DOI：
10.1002/embr.201337945
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发表时间：
2014-04
期刊：
影响因子：
7.7
通讯作者：
Suzuki, Ken
中科院分区：
文献类型：
--
作者：
Shintani, Yasunori;Drexler, Hannes C. A.;Kioka, Hidetaka;Terracciano, Cesare M. N.;Coppen, Steven R.;Imamura, Hiromi;Akao, Masaharu;Nakai, Junichi;Wheeler, Ann P.;Higo, Shuichiro;Nakayama, Hiroyuki;Takashima, Seiji;Yashiro, Kenta;Suzuki, Ken
toll样受体9 （TLR9）在感染背景下识别病原体DNA和受损细胞释放的细胞DNA中起关键作用。免疫细胞中的促炎性TLR9信号通路已经得到了很好的研究，但我们最近发现了TLR9暂时减少能量底物以诱导心肌细胞和神经元对应激的细胞保护的另一种途径。然而，TLR9刺激减少能量底物的机制尚不清楚。在这里，我们发现钙转运atp酶SERCA2（也称为Atp2a2）是TLR9信号通路的关键分子。TLR9刺激降低SERCA2活性，调节SR/ER和线粒体之间的Ca2+处理，从而导致线粒体ATP水平降低和细胞保护机制的激活。这些发现揭示了免疫细胞和非免疫细胞（包括心肌细胞）使用相同的配体-受体系统是如何引起不同的先天反应的。
Toll-like receptor 9 (TLR9) has a key role in the recognition of pathogen DNA in the context of infection and cellular DNA that is released from damaged cells. Pro-inflammatory TLR9 signalling pathways in immune cells have been well investigated, but we have recently discovered an alternative pathway in which TLR9 temporarily reduces energy substrates to induce cellular protection from stress in cardiomyocytes and neurons. However, the mechanism by which TLR9 stimulation reduces energy substrates remained unknown. Here, we identify the calcium-transporting ATPase, SERCA2 (also known as Atp2a2), as a key molecule for the alternative TLR9 signalling pathway. TLR9 stimulation reduces SERCA2 activity, modulating Ca2+ handling between the SR/ER and mitochondria, which leads to a decrease in mitochondrial ATP levels and the activation of cellular protective machinery. These findings reveal how distinct innate responses can be elicited in immune and non-immune cells—including cardiomyocytes—using the same ligand-receptor system.
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影响因子：
64.5
作者：
Cárdenas C;Miller RA;Smith I;Bui T;Molgó J;Müller M;Vais H;Cheung KH;Yang J;Parker I;Thompson CB;Birnbaum MJ;Hallows KR;Foskett JK
通讯作者：
Foskett JK
影响因子：
2.9
作者：
Glancy, Brian;Balaban, Robert S.
通讯作者：
Balaban, Robert S.
DOI：
10.1073/pnas.1219243110
发表时间：
2013-03-26
影响因子：
11.1
作者：
Shintani, Yasunori;Kapoor, Amar;Suzuki, Ken
通讯作者：
Suzuki, Ken
DOI：
10.1073/pnas.0408030101
发表时间：
2004-12-14
影响因子：
11.1
作者：
Palmer, AE;Jin, C;Tsien, RY
通讯作者：
Tsien, RY
影响因子：
4.1
作者：
EGGERMONT, JA;WUYTACK, F;CASTEELS, R
通讯作者：
CASTEELS, R