2. Academic Validation
  3. Controlling mitochondrial membrane architecture via MIC60 determines viral replication to promote anti-viral immunity

Controlling mitochondrial membrane architecture via MIC60 determines viral replication to promote anti-viral immunity

  • Cell Rep. 2025 Jul 22;44(7):115922. doi: 10.1016/j.celrep.2025.115922.
Ichiro Katahira 1,  Nina Liebrand 1,  Michal Gorzkiewicz 1,  Niklas Paul Klahm 2,  Džiuljeta Abromavičiūtė 1,  Julia Werner 1,  Karina Stephanie Krings 1,  Sarah Orywol 1,  Tobias Lautwein 3,  Karl Köhrer 3,  Diran Herebian 4,  Ertan Mayatepek 4,  Max Anstötz 5,  Ann Kathrin Bergmann 6,  Arun Kumar Kondadi 2,  Haifeng C Xu 1,  Aleksandra A Pandyra 7,  Takumi Kobayashi 8,  Dirk Brenner 9,  Thomas Floss 10,  Ulrich Kalinke 11,  Andreas S Reichert 2,  Philipp A Lang 12
Affiliations

Affiliations

  • 1 Department of Molecular Medicine II, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Universitätsstrasse 1, Düsseldorf 40225, Germany.
  • 2 Institute of Biochemistry and Molecular Biology I, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Universitätsstrasse 1, Düsseldorf 40225, Germany.
  • 3 Biological and Medical Research Center (BMFZ), Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, Düsseldorf D-40225, Germany.
  • 4 Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
  • 5 Institute of Anatomy II, Medical Faculty and University Hospital, Heinrich Heine University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
  • 6 Core Facility for Electron Microscopy, Faculty of Medicine, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
  • 7 Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Venusberg-Campus 1, Bonn 53127, Germany; German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany; University Hospital Düsseldorf, Department of Oncology, Hematology and Clinical Immunology, Moorenstrasse 5, Düsseldorf 40225, Germany.
  • 8 Experimental and Molecular Immunology, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg; Immunology & Genetics, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts Fourneaux, Esch-sur-Alzette, Luxembourg.
  • 9 Experimental and Molecular Immunology, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg; Immunology & Genetics, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts Fourneaux, Esch-sur-Alzette, Luxembourg; Odense Research Center for Anaphylaxis (ORCA), Department of Dermatology and Allergy Center, Odense University Hospital, University of Southern Denmark, Odense, Denmark.
  • 10 Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt, Neuherberg, Germany.
  • 11 Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.
  • 12 Department of Molecular Medicine II, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Universitätsstrasse 1, Düsseldorf 40225, Germany. Electronic address: langp@uni-duesseldorf.de.
PMID: 40628273 DOI: 10.1016/j.celrep.2025.115922
Abstract

Virus-infected cells often exhibit dramatic cellular changes accompanied by altered mitochondrial function. The contribution of factors shaping the inner mitochondrial membrane (IMM) and cristae architecture to viral replication is insufficiently understood. Single-cell transcriptomics applying vesicular stomatitis virus Infection suggests involvement of factors determining IMM architecture following Infection. Consistently, inhibition of the F1FO adenosine triphosphate (ATP) synthase reduces viral replication, which is associated with oligomerization of this complex and altered IMM structure. Moreover, deletion of mitochondrial contact site and cristae organizing system (MICOS) complex by targeting MIC60 results in reduced viral replication. Generation of Mic60inv/invCD11c-Cre+ mice uncovers reduced crista junctions and viral replication in bone marrow-derived dendritic cells. Consequently, reduced viral replication in CD11c-expressing cells limits prolonged immune activation. Altogether, by linking the F1FO ATP Synthase and the MICOS complex to viral replication and immune activation, we describe links between the mitochondrial structure-metabolism and the immune response against viral Infection.

Keywords

BMDC; CP: Cell biology; CP: Microbiology; MIC60; MICOS; immunometabolism; innate immunity; inner mitochondrial membrane; itaconate; mitochondria; viral infection.

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