Listeria monocytogenesexploits the MICOS complex subunit Mic10 to promote mitochondrial fragmentation and cellular infection

Autor: Mariette Matondo, Pascale Cossart, Filipe Carvalho, Fabrizia Stavru, Anna Spier, T. Chaze
Přispěvatelé: Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology (UTechS MSBio), Institut Pasteur [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), This study was supported by grants to P.C. from the European Research Council (H2020-ERC-2014-409ADG 670823-BacCellEpi), the Agence Nationale de la Recherche (ANR) and the French Government’s 'Investissements d’Avenir' program Laboratoires d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (LabEx IBEID, ANR-10-LABX-62-IBEID). A.S. was supported by a BioSPC doctoral fellowship from the Université Paris Diderot. P.C. is a Senior International Research Scholar of the Howard Hughes Medical Institute. F.S. is a CNRS permanent researcher, We thank current and past lab members for helpful discussions, Francis Impens and Evy Timmerman (VIB Proteomics Core, University of Ghent, Belgium) for training and assistance with proteomic analyses, and Alessandro Pagliuso for critical reading of the manuscript, ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 670823,H2020,ERC-2014-ADG,BacCellEpi(2015), Centre National de la Recherche Scientifique (CNRS)-Centre de Ressources et de Recherche Technologique - Center for Technological Resources and Research (C2RT), Institut Pasteur [Paris]-Institut Pasteur [Paris], ANR-10-LABX-62-IBEID,IBEID,Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Stavru, Fabrizia, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Bacterial, cellular and epigenetic factors that control enteropathogenicity - BacCellEpi - - H20202015-10-01 - 2018-09-30 - 670823 - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA)
Rok vydání: 2019
Předmět:
Mic10
MESH: HCT116 Cells
MESH: Mitochondria
[SDV]Life Sciences [q-bio]
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Mitochondrion
Biology
MESH: Listeria monocytogenes
medicine.disease_cause
03 medical and health sciences
proteomics
0302 clinical medicine
Listeria monocytogenes
Organelle
MESH: Up-Regulation
medicine
Inner mitochondrial membrane
[SDV.BC] Life Sciences [q-bio]/Cellular Biology
[SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology
030304 developmental biology
0303 health sciences
MESH: Humans
MICOS complex
mitochondrial fission
MESH: Proteomics
Listeriolysin O
MESH: Mitochondrial Proteins
MESH: Mitochondrial Dynamics
Cell biology
[SDV] Life Sciences [q-bio]
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology
Mitochondrial fission
MESH: Membrane Proteins
030217 neurology & neurosurgery
Intracellular
Zdroj: mBio
mBio, American Society for Microbiology, 2020, 11 (1), ⟨10.1128/mBio.03171-19⟩
mBio, 2020, 11 (1), ⟨10.1128/mBio.03171-19⟩
ISSN: 2161-2129
2150-7511
DOI: 10.1101/712067
Popis: 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 non-physiological cues. We previously showed that infection with the human bacterial pathogenListeria monocytogeneselicits transient mitochondrial fission and a drop in mitochondrial-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 inL. monocytogenes-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-deficientL. monocytogenes. Increased mitochondrial Mic10 levels did not correlate with upregulated transcription, suggesting a post-transcriptional regulation. We showed that Mic10 is necessary forL. monocytogenes-induced mitochondrial network fragmentation, and that it contributes toL. monocytogenescellular infection independently of MICOS proteins Mic13, Mic26 and Mic27. Together,L. monocytogenesinfection allowed us to uncover a role for Mic10 in mitochondrial fission.ImportancePathogenic 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 thatListeria monocytogenesinfection impairs mitochondrial function and triggers fission of the mitochondrial network at an early infection stage, in a process that is independent of the main mitochondrial fission protein Drp1. Here, we analyzed how mitochondrial proteins change in response toL. monocytogenesinfection 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 forL. monocytogenes-dependent mitochondrial fission and infection of host cells. Our findings thus offer new insight into the mechanisms used byL. monocytogenesto hijack mitochondria to optimize host infection.
Databáze: OpenAIRE
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