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In this study, the underlying molecular mechanisms are aimed to clarify through which <jats:italic>Listeria monocytogenes<\/jats:italic> (<jats:italic>L. monocytogenes<\/jats:italic>), a human bacterial pathogen, manipulates mitochondrial dynamics to enhance its pathogenicity. It is demonstrated that <jats:italic>L. monocytogenes<\/jats:italic> triggers transient mitochondrial fission through its virulence factor listeriolysin O (LLO), driven by LLO's interaction with Mic60, a core component of the mitochondrial contact site and the cristae organizing system (MICOS). Specifically, Phe251 within LLO is identify as a crucial residue for binding to Mic60, crucial for LLO\u2010induced mitochondrial fragmentation and bacterial pathogenicity. Importantly, it is that Mic60 affect the formation of F\u2010actin tails recruited by <jats:italic>L. monocytogenes<\/jats:italic>, thereby contributing to intracellular bacterial infection. Mic60 plays a critical role in mediating changes in mitochondrial morphology, membrane potential, and reactive oxidative species (ROS) production, and <jats:italic>L. monocytogenes<\/jats:italic> infection exacerbates these changes by affecting Mic60 expression. These findings unveil a novel mechanism through which intracellular bacteria exploit host mitochondria, shedding light on the complex interplay between hosts and microbes during infections. This knowledge holds promise for developing innovative strategies to combat bacterial infections.<\/jats:p>","DOI":"10.1002\/advs.202406760","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T06:46:10Z","timestamp":1729493170000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The MICOS Complex Subunit Mic60 is Hijacked by Intracellular Bacteria to Manipulate Mitochondrial Dynamics and Promote Bacterial Pathogenicity"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7530-5605","authenticated-orcid":false,"given":"Changyong","family":"Cheng","sequence":"first","affiliation":[{"name":"Key Laboratory of Applied Technology on Green\u2010Eco\u2010Healthy Animal Husbandry of Zhejiang Province Zhejiang Provincial Engineering Research Center for Animal Health Diagnostics &amp; Advanced Technology Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management China\u2010Australia Joint Laboratory for Animal Health Big Data Analytics College of Veterinary Medicine of Zhejiang A&amp;F University  666 Wusu Street, Lin'an District Hangzhou Zhejiang Province..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mianmian","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Applied Technology on Green\u2010Eco\u2010Healthy Animal Husbandry of Zhejiang Province Zhejiang Provincial Engineering Research Center for Animal Health Diagnostics &amp; 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