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

Amini, Poorya; Stojkov, Darko; Felser, Andrea; Jackson, Christopher B; Courage, Carolina; Schaller, André; Gelman, Laurent; Soriano, Maria Eugenia; Nuoffer, Jean-Marc; Scorrano, Luca; Benarafa, Charaf; Yousefi, Shida; Simon, Hans-Uwe (2018). Neutrophil extracellular trap formation requires OPA1-dependent glycolytic ATP production. Nature communications, 9(1), p. 2958. Nature Publishing Group 10.1038/s41467-018-05387-y

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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 (Opa1), 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 Opa1 mice exhibit a reduced antibacterial defense capability against Pseudomonas aeruginosa.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Humangenetik
09 Interdisciplinary Units > Microscopy Imaging Center MIC

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Amini, Poorya; Stojkov, Darko; Felser, Andrea Debora; Courage, Carolina; Schaller, André; Nuoffer, Jean-Marc; Benarafa, Charaf; Yousefi, Shida and Simon, Hans-Uwe

Subjects:

600 Technology > 630 Agriculture
600 Technology > 610 Medicine & health

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Sabrina Cookman

Date Deposited:

05 Sep 2018 17:21

Last Modified:

05 Feb 2019 15:08

Publisher DOI:

10.1038/s41467-018-05387-y

PubMed ID:

30054480

BORIS DOI:

10.7892/boris.119804

URI:

https://boris.unibe.ch/id/eprint/119804

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