Listeria monocytogenes upregulates mitochondrial calcium signalling to inhibit LC3-associated phagocytosis as a survival strategy.
Listeria monocytogenes upregulates mitochondrial calcium signalling to inhibit LC3-associated phagocytosis as a survival strategy.
复制标题
DOI：
10.1038/s41564-020-00843-2
复制
发表时间：
2021-03
影响因子：
28.3
通讯作者：
Wen H
中科院分区：
文献类型：
--
作者：
Li T;Kong L;Li X;Wu S;Attri KS;Li Y;Gong W;Zhao B;Li L;Herring LE;Asara JM;Xu L;Luo X;Lei YL;Ma Q;Seveau S;Gunn JS;Cheng X;Singh PK;Green DR;Wang H;Wen H
线粒体被认为起源于约25亿年前。除了在细胞中产生能量外，线粒体在防御细菌病原体方面也有作用。尽管线粒体的形态和功能在细菌的挑战下发生了深刻的变化，但细胞内细菌是否可以劫持线粒体以促进其生存仍然是难以捉摸的。我们报告说，李斯特菌，细胞内的细菌病原体，抑制LC 3-相关的吞噬作用（ESTA）的线粒体Ca 2+信号的调制，以生存在细胞内。L.单核细胞增多症通过线粒体Ca 2+单向转运体（MCU）诱导线粒体Ca 2+摄取，这反过来增加丙酮酸脱氢酶（PDH）产生乙酰辅酶A（乙酰辅酶A）。用乙酰辅酶A乙酰化转录因子Rubicon减少了转录因子的形成。MCU的基因消融由于增加的细菌形成而减弱细胞内细菌生长。我们的数据表明，线粒体Ca 2+信号的调节可以增加细胞内细菌的存活率，并突出了线粒体代谢在宿主-微生物相互作用中的重要性。
Mitochondria are believed to have originated ~2.5 billion years ago. As well as energy generation in cells, mitochondria have a role in defense against bacterial pathogens. Despite profound changes in mitochondrial morphology and functions upon bacterial challenge, whether intracellular bacteria can hijack mitochondria to promote their survival remains elusive. We report that Listeria monocytogenes, an intracellular bacterial pathogen, suppresses LC3-associated phagocytosis (LAP) by modulation of mitochondrial Ca2+ signaling in order to survive inside cells. Invasion of macrophages by L. monocytogenes induced mitochondrial Ca2+ uptake through the mitochondrial Ca2+ uniporter (MCU), which in turn increased acetyl-coenzyme A (acetyl-CoA) production by pyruvate dehydrogenase (PDH). Acetylation of LAP effector Rubicon with acetyl-CoA decreased LAP formation. Genetic ablation of MCU attenuated intracellular bacterial growth due to increased LAP formation. Our data show that modulation of mitochondrial Ca2+ signaling can increase bacterial survival inside cells, and highlights the importance of mitochondrial metabolism in host-microbial interactions.
登录
查看更多内容
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
64.8
作者：
Bambouskova M;Gorvel L;Lampropoulou V;Sergushichev A;Loginicheva E;Johnson K;Korenfeld D;Mathyer ME;Kim H;Huang LH;Duncan D;Bregman H;Keskin A;Santeford A;Apte RS;Sehgal R;Johnson B;Amarasinghe GK;Soares MP;Satoh T;Akira S;Hai T;de Guzman Strong C;Auclair K;Roddy TP;Biller SA;Jovanovic M;Klechevsky E;Stewart KM;Randolph GJ;Artyomov MN
通讯作者：
Artyomov MN
内膜的四十千克蛋白是线粒体钙Uniporter。
影响因子：
64.8
作者：
De Stefani, Diego;Raffaello, Anna;Teardo, Enrico;Szabo, Ildiko;Rizzuto, Rosario
通讯作者：
Rizzuto, Rosario
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
29
作者：
Arts RJ;Novakovic B;Ter Horst R;Carvalho A;Bekkering S;Lachmandas E;Rodrigues F;Silvestre R;Cheng SC;Wang SY;Habibi E;Gonçalves LG;Mesquita I;Cunha C;van Laarhoven A;van de Veerdonk FL;Williams DL;van der Meer JW;Logie C;O'Neill LA;Dinarello CA;Riksen NP;van Crevel R;Clish C;Notebaart RA;Joosten LA;Stunnenberg HG;Xavier RJ;Netea MG
通讯作者：
Netea MG