Neutrophil extracellular trap formation requires OPA1-dependent glycolytic ATP production.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30054480.
- Also identified by DOI 10.1038/s41467-018-05387-y and PMC identifier 6063938.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 (Opa1<sup>N∆</sup>), 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<sup>+</sup> 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<sup>N∆</sup> mice exhibit a reduced antibacterial defense capability against Pseudomonas aeruginosa.
Medical subject headings
- Adenosine Triphosphate
- Extracellular Traps
- GTP Phosphohydrolases
- Glycolysis
- Neutrophils