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Legionella pneumophila Modulates Mitochondrial Dynamics to Trigger Metabolic Repurposing of Infected Macrophages

Abstract : 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.
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Submitted on : Thursday, January 18, 2018 - 4:26:30 PM
Last modification on : Tuesday, November 22, 2022 - 2:26:15 PM
Long-term archiving on: : Wednesday, May 23, 2018 - 10:56:59 PM

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Pedro Escoll, Ok-Ryul Song, Flávia Viana, Bernhard Steiner, Thibault Lagache, et al.. Legionella pneumophila Modulates Mitochondrial Dynamics to Trigger Metabolic Repurposing of Infected Macrophages. Cell Host and Microbe, 2017, 22 (3), pp.302-316.e7. ⟨10.1016/j.chom.2017.07.020⟩. ⟨pasteur-01687682⟩

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