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

Ichiro Katahira, Nina Liebrand, Michal Gorzkiewicz, Niklas Paul Klahm, Džiuljeta Abromavičiūtė, Julia Werner, Karina Stephanie Krings, Sarah Orywol, Tobias Lautwein, Karl Köhrer, Diran Herebian, Ertan Mayatepek, Max Anstötz, Ann Kathrin Bergmann, Arun Kumar Kondadi, Haifeng C. Xu, Aleksandra A. Pandyra, Takumi Kobayashi, Dirk Brenner, Thomas FlossUlrich Kalinke, Andreas S. Reichert, Philipp A. Lang*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

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/inv CD11c-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.

Original languageEnglish
Article number115922
Number of pages26
JournalCell Reports
Volume44
Issue number7
Early online date1 Jul 2025
DOIs
Publication statusPublished - 22 Jul 2025

Keywords

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

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