Unexpected function of the phagocyte NADPH oxidase in supporting hyperglycolysis in stimulated neutrophils: key role of 6‐phosphofructo‐2‐kinase. Issue 2 (31st October 2016)

• Record Type: Journal Article
• Authors: Baillet, Athan; Hograindleur, Marc‐André; El Benna, Jamel; Grichine, Alexei; Berthier, Sylvie; Morel, Françoise; Paclet, Marie‐Hélèene
• Is Part Of: FASEB journal. Volume 31:Issue 2(2017)
• Page Start: 663
• Page End: 673
• Publication Date: 2016-10-31
• Subjects: Nox2 -- PMN -- PFK‐2 -- reactive oxygen species -- energetic metabolism; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201600720R
• Languages: English
• ISSNs: 0892-6638

Abstract

ABSTRACT: The phagocyte NADPH oxidase 2 (Nox2) is an enzymatic complex that is involved in innate immunity, notably via its capacity to produce toxic reactive oxygen species. Recently, a proteomic analysis of the constitutively active Nox2 complex, isolated from neutrophil fractions, highlighted the presence of 6‐phosphofructo‐2‐kinase (PFK‐2). The purpose of this workwas to study the relationship between PFK‐2 and NADPHoxidase in neutrophils. Data have underlined a specific association of the active phosphorylated form of PFK‐2 with Nox2 complex in stimulated neutrophils. In its active form, PFK‐2 catalyzes the production of fructose‐2, 6‐bisphosphate, which is the main allosteric activator of phosphofructo‐1‐kinase, the limiting enzyme in glycolysis. Pharmacologic inhibition of PFK‐2 phosphorylation and cell depletion in PFK‐2 by a small interfering RNA strategy led to a decrease in the glycolysis rate and a reduction in NADPH oxidase activity in stimulated cells. Surprisingly, alteration of Nox2 activity impacted the glycolysis rate, which indicated that Nox2 in neutrophils was not only required for reactive oxygen species production but was also involved in supporting the energeticmetabolismincrease thatwas induced by inflammatory conditions. PFK‐2 seems to be a strategic element that links NADPH oxidase activation and glycolysismodulation, and, as such, is proposedas a potential therapeutic target in inflammatory diseases.—Baillet, A., Hograindleur, M.‐A., El Benna, J., Grichine, A., Berthier, S., Morel, F., Paclet, M.‐H. Unexpected function of the phagocyteNADPHoxidase in supporting hyperglycolysis in stimulated neutrophils:key role of 6‐phosphofructo‐2‐ kinase. FASEB J. 31, 663–673 (2017). www.fasebj.org