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Neutrophil extracellular trap formation requires OPA1-dependent glycolytic ATP production

Author

Listed:
  • Poorya Amini

    (Institute of Pharmacology, University of Bern)

  • Darko Stojkov

    (Institute of Pharmacology, University of Bern)

  • Andrea Felser

    (University Institute of Clinical Chemistry, Bern University Hospital)

  • Christopher B. Jackson

    (Biomedicum Helsinki, University of Helsinki)

  • Carolina Courage

    (Inselspital, Bern University Hospital, University of Bern)

  • André Schaller

    (Inselspital, Bern University Hospital, University of Bern)

  • Laurent Gelman

    (Friedrich Miescher Institute for Biomedical Research)

  • Maria Eugenia Soriano

    (University of Padua)

  • Jean-Marc Nuoffer

    (University Institute of Clinical Chemistry, Bern University Hospital)

  • Luca Scorrano

    (Venetian Institute of Molecular Medicine (VIMM))

  • Charaf Benarafa

    (Institute of Virology and Immunology
    Department of Infectious Diseases and Pathology, Vetsuisse Faculty, University of Bern)

  • Shida Yousefi

    (Institute of Pharmacology, University of Bern)

  • Hans-Uwe Simon

    (Institute of Pharmacology, University of Bern)

Abstract

Optic atrophy 1 (OPA1) is a mitochondrial inner membrane protein that has an important role in mitochondrial fusion and structural integrity. Dysfunctional OPA1 mutations cause atrophy of the optic nerve leading to blindness. Here, we show that OPA1 has an important role in the innate immune system. Using conditional knockout mice lacking Opa1 in neutrophils (Opa1N∆), we report that lack of OPA1 reduces the activity of mitochondrial electron transport complex I in neutrophils. This then causes a decline in adenosine-triphosphate (ATP) production through glycolysis due to lowered NAD+ availability. Additionally, we show that OPA1-dependent ATP production in these cells is required for microtubule network assembly and for the formation of neutrophil extracellular traps. Finally, we show that Opa1N∆ mice exhibit a reduced antibacterial defense capability against Pseudomonas aeruginosa.

Suggested Citation

  • Poorya Amini & Darko Stojkov & Andrea Felser & Christopher B. Jackson & Carolina Courage & André Schaller & Laurent Gelman & Maria Eugenia Soriano & Jean-Marc Nuoffer & Luca Scorrano & Charaf Benarafa, 2018. "Neutrophil extracellular trap formation requires OPA1-dependent glycolytic ATP production," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05387-y
    DOI: 10.1038/s41467-018-05387-y
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