Legionella pneumophila Modulates Mitochondrial Dynamics to Trigger Metabolic Repurposing of Infected Macrophages
Legionella pneumophila Modulates Mitochondrial Dynamics to Trigger Metabolic Repurposing of Infected Macrophages
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DOI：
10.1016/j.chom.2017.07.020
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发表时间：
2017-09-13
影响因子：
30.3
通讯作者：
Buchrieser, Carmen
中科院分区：
文献类型：
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作者：
Escoll, Pedro;Song, Ok-Ryul;Buchrieser, Carmen
胞内细菌嗜肺军团菌编码 IV 型分泌系统 (T4SS)，该系统将效应蛋白注入巨噬细胞，以便在含有军团菌的液泡 (LCV) 内建立和复制。 LCV 一旦产生，就会通过尚不清楚的机制与线粒体相互作用。我们发现军团菌使用 T4SS 独立和 T4SS 依赖机制分别与线粒体相互作用并诱导线粒体断裂，最终改变线粒体代谢。 T4SS 效应器 MitF 是一种 Ran GTP 酶激活剂，是线粒体网络裂变所必需的。 MitF 的这些作用是通过线粒体 DNM1L 的积累而发生的，DNM1L 是一种对裂变至关重要的 GTP 酶。此外，线粒体呼吸以 T4SS 依赖性方式突然停止，而 T4SS 独立的细胞糖酵解上调仍然升高。总的来说，线粒体动力学的这些改变促进了巨噬细胞中类似 Warburg 的表型，有利于细菌复制。因此，重新连接细胞生物能以在宿主细胞中创建复制许可的生态位是嗜肺军团菌的毒力策略。
The intracellular bacteria Legionella pneumophila encodes a type IV secretion system (T4SS) that injects effector proteins into macrophages in order to establish and replicate within the Legionella-containing vacuole (LCV). Once generated, the LCV interacts with mitochondria through unclear mechanisms. We show that Legionella uses both T4SS-independent and T4SS-dependent mechanisms to respectively interact with mitochondria and induce mitochondrial fragmentation that ultimately alters mitochondrial metabolism. The T4SS effector MitF, a Ran GTPase activator, is required for fission of the mitochondrial network. These effects of MitF occur through accumulation of mitochondrial DNM1L, a GTPase critical for fission. Furthermore mitochondrial respiration is abruptly halted in a T4SS-dependent manner, while T4SS-independent upregulation of cellular glycolysis remains elevated. Collectively, these alterations in mitochondrial dynamics promote a Warburg-like phenotype in macrophages that favors bacterial replication. Hence the rewiring of cellular bioenergetics to create a replication permissive niche in host cells is a virulence strategy of L. pneumophila.