Controlling mitochondrial membrane architecture via MIC60 determines viral replication to promote anti-viral immunity
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 F<sub>1</sub>F<sub>O</sub> 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 Mic60<sup>inv/inv</sup>CD11c-Cre<sup>+</sup> 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 F<sub>1</sub>F<sub>O</sub> 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.
Authors
- Philipp A. Lang (ORCID: https://orcid.org/0000-0001-5341-0407)
- Andreas S. Reichert (ORCID: https://orcid.org/0000-0001-9340-3113)
- Ulrich Kalinke (ORCID: https://orcid.org/0000-0003-0503-9564)
- Thomas Floß (ORCID: https://orcid.org/0000-0002-1445-1465)
- Diran Agaid Herebian (ORCID: https://orcid.org/0000-0002-8528-0122)
- Aleksandra A. Pandyra (ORCID: https://orcid.org/0000-0003-4794-0035)
- Julia Werner (ORCID: https://orcid.org/0000-0001-7407-8490)
- Ertan Mayatepek (ORCID: https://orcid.org/0000-0001-8460-3738)
- Ann Kathrin Bergmann
- Karl Köhrer (ORCID: https://orcid.org/0000-0003-3644-2022)
- Arun Kumar Kondadi (ORCID: https://orcid.org/0000-0002-5888-7834)
- Dirk Brenner (ORCID: https://orcid.org/0000-0001-8979-1045)
- Max Anstötz (ORCID: https://orcid.org/0000-0003-3071-5835)
- Michał Gorzkiewicz (ORCID: https://orcid.org/0000-0001-9258-3626)
- T Kobayashi (ORCID: https://orcid.org/0000-0002-6466-5082)
- Ichiro Katahira (ORCID: https://orcid.org/0009-0004-9353-1886)
- Tobias Lautwein (ORCID: https://orcid.org/0000-0002-3872-3613)
- Niklas Paul Klahm
- Karina S. Krings (ORCID: https://orcid.org/0000-0001-6519-1395)
- Džiuljeta Abromavičiūtė (ORCID: https://orcid.org/0009-0001-4451-7031)
- Haifeng C. Xu (ORCID: https://orcid.org/0000-0002-4674-4983)
- Nina Liebrand
- Sarah Orywol
Institutions
- Helmholtz Zentrum München (DE)
- Medizinische Hochschule Hannover (DE)
- Düsseldorf University Hospital (DE)
- Helmholtz Centre for Infection Research (DE)
- Center for Experimental and Clinical Infection Research (DE)
- Heinrich Heine University Düsseldorf (DE)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-07-01
- DOI
- https://doi.org/10.1016/j.celrep.2025.115922
- Citations
- 1
- Primary Topic
- interferon and immune responses
- Type
- article
- Field-Weighted Citation Impact
- 0.80