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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 | Hans-Uwe Simon
Nature communications | 2018

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.

Pubmed ID: 30054480

Associated grants

  • Agency: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation), International
    Id: 310030_166473

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