Pharmacology and Clinical Pharmacology

Neutrophil extracellular trap formation requires OPA1-dependent glycolytic ATP production

Prof. Dr. Hans-Uwe Simon, University of Bern

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. The research team shows that OPA1 has an important role in the innate immune system. Using conditional knockout mice lacking Opa1 in neutrophils (Opa1NΔ), they 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, they show that OPA1-dependent ATP production in these cells is required for microtubule network assembly and for the formation of neutrophil extracellular traps. Finally, they show that Opa1NΔ mice exhibit a reduced antibacterial defense capability against Pseudomonas aeruginosa.