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Nat Commun. 2018 Jul 27;9(1):2958. doi: 10.1038/s41467-018-05387-y.

Neutrophil extracellular trap formation requires OPA1-dependent glycolytic ATP production.

Author information

1
Institute of Pharmacology, University of Bern, 3010, Bern, Switzerland.
2
University Institute of Clinical Chemistry, Bern University Hospital, 3010, Bern, Switzerland.
3
Research Program for Molecular Neurology, Biomedicum Helsinki, University of Helsinki, 00290, Helsinki, Finland.
4
Division of Human Genetics and Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, 3010, Bern, Switzerland.
5
Friedrich Miescher Institute for Biomedical Research, 4058, Basel, Switzerland.
6
Department of Biology, University of Padua, 35121, Padua, Italy.
7
Venetian Institute of Molecular Medicine (VIMM), 35129, Padua, Italy.
8
Institute of Virology and Immunology, 3147, Mittelhäusern, Switzerland.
9
Department of Infectious Diseases and Pathology, Vetsuisse Faculty, University of Bern, 3012, Bern, Switzerland.
10
Institute of Pharmacology, University of Bern, 3010, Bern, Switzerland. hus@pki.unibe.ch.

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.

PMID:
30054480
PMCID:
PMC6063938
DOI:
10.1038/s41467-018-05387-y
[Indexed for MEDLINE]
Free PMC Article

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