Unité des Interactions Bactéries-Cellules, Institut Pasteur, Paris, France.
Institut National de la Santé et de la Recherche Médicale (INSERM), U604, Paris, France.
mBio. 2020 Feb 4;11(1):e03171-19. doi: 10.1128/mBio.03171-19.
Mitochondrial function adapts to cellular demands and is affected by the ability of the organelle to undergo fusion and fission in response to physiological and nonphysiological cues. We previously showed that infection with the human bacterial pathogen elicits transient mitochondrial fission and a drop in mitochondrion-dependent energy production through a mechanism requiring the bacterial pore-forming toxin listeriolysin O (LLO). Here, we performed quantitative mitochondrial proteomics to search for host factors involved in -induced mitochondrial fission. We found that Mic10, a critical component of the mitochondrial contact site and cristae organizing system (MICOS) complex, is significantly enriched in mitochondria isolated from cells infected with wild-type but not with LLO-deficient Increased mitochondrial Mic10 levels did not correlate with upregulated transcription, suggesting a posttranscriptional mechanism. We then showed that Mic10 is necessary for -induced mitochondrial network fragmentation and that it contributes to cellular infection independently of MICOS proteins Mic13, Mic26, and Mic27. In conclusion, investigation of infection allowed us to uncover a role for Mic10 in mitochondrial fission. Pathogenic bacteria can target host cell organelles to take control of key cellular processes and promote their intracellular survival, growth, and persistence. Mitochondria are essential, highly dynamic organelles with pivotal roles in a wide variety of cell functions. Mitochondrial dynamics and function are intimately linked. Our previous research showed that infection impairs mitochondrial function and triggers fission of the mitochondrial network at an early infection stage, in a process that is independent of the presence of the main mitochondrial fission protein Drp1. Here, we analyzed how mitochondrial proteins change in response to infection and found that infection raises the levels of Mic10, a mitochondrial inner membrane protein involved in formation of cristae. We show that Mic10 is important for -dependent mitochondrial fission and infection of host cells. Our findings thus offer new insight into the mechanisms used by to hijack mitochondria to optimize host infection.
线粒体功能可适应细胞需求，并受细胞器在响应生理和非生理信号时融合和裂变能力的影响。我们之前的研究表明，感染人类细菌病原体李斯特菌会引发短暂的线粒体裂变，并通过一种需要细菌孔形成毒素李斯特菌溶血素 O（LLO）的机制导致依赖线粒体的能量产生下降。在这里，我们进行了定量线粒体蛋白质组学研究，以寻找参与李斯特菌诱导的线粒体裂变的宿主因素。我们发现，线粒体接触点和嵴组织系统（MICOS）复合物的关键组成部分 Mic10，在感染野生型李斯特菌而非 LLO 缺陷型李斯特菌的细胞中分离的线粒体中显著富集。增加的线粒体 Mic10 水平与上调的转录并不相关，这表明存在转录后机制。然后，我们表明 Mic10 是李斯特菌诱导的线粒体网络碎片化所必需的，并且它独立于 MICOS 蛋白 Mic13、Mic26 和 Mic27 有助于李斯特菌细胞感染。总之，对李斯特菌感染的研究揭示了 Mic10 在线粒体裂变中的作用。致病菌可以靶向宿主细胞细胞器来控制关键的细胞过程并促进其在细胞内的存活、生长和持续存在。线粒体是必不可少的、高度动态的细胞器，在广泛的细胞功能中具有关键作用。线粒体动力学和功能密切相关。我们之前的研究表明，李斯特菌感染会损害线粒体功能，并在早期感染阶段触发线粒体网络的裂变，这一过程独立于主要的线粒体裂变蛋白 Drp1 的存在。在这里，我们分析了线粒体蛋白如何响应李斯特菌感染而发生变化，并发现感染会提高 Mic10 的水平，Mic10 是一种参与嵴形成的线粒体内膜蛋白。我们表明 Mic10 对李斯特菌依赖性线粒体裂变和宿主细胞感染很重要。因此，我们的研究结果为李斯特菌劫持线粒体以优化宿主感染所使用的机制提供了新的见解。
