Neutrophil extracellular trap formation requires OPA1-dependent glycolytic ATP production

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, Shida Yousefi and Hans-Uwe Simon ()
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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
Shida Yousefi: Institute of Pharmacology, University of Bern
Hans-Uwe Simon: Institute of Pharmacology, University of Bern

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-05387-y

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