Phosphorylation of PFKL regulates metabolic reprogramming in macrophages following pattern recognition receptor activation

Meiyue Wang, Heinrich Flaswinkel, Abhinav Joshi, Matteo Napoli, Sergi Masgrau-Alsina, Julia M. Kamper, Antonia Henne, Alexander Heinz, Marleen Berouti, Niklas A. Schmacke, Karsten Hiller, Elisabeth Kremmer, Benedikt Wefers, Wolfgang Wurst, Markus Sperandio, Jürgen Ruland, Thomas Fröhlich and Veit Hornung ()
Additional contact information
Meiyue Wang: Ludwig-Maximilians-Universität München
Heinrich Flaswinkel: Ludwig-Maximilians-Universität München
Abhinav Joshi: Technische Universität München
Matteo Napoli: Cardiovascular Physiology and Pathophysiology, Ludwig-Maximilians-Universität München
Sergi Masgrau-Alsina: Cardiovascular Physiology and Pathophysiology, Ludwig-Maximilians-Universität München
Julia M. Kamper: Ludwig-Maximilians-Universität München
Antonia Henne: Biotechnology and Bioinformatics, Technische Universität Braunschweig
Alexander Heinz: Biotechnology and Bioinformatics, Technische Universität Braunschweig
Marleen Berouti: Ludwig-Maximilians-Universität München
Niklas A. Schmacke: Ludwig-Maximilians-Universität München
Karsten Hiller: Biotechnology and Bioinformatics, Technische Universität Braunschweig
Elisabeth Kremmer: Ludwig-Maximilians-Universität München
Benedikt Wefers: Helmholtz Zentrum München
Wolfgang Wurst: Helmholtz Zentrum München
Markus Sperandio: Cardiovascular Physiology and Pathophysiology, Ludwig-Maximilians-Universität München
Jürgen Ruland: Technische Universität München
Thomas Fröhlich: Ludwig-Maximilians-Universität München
Veit Hornung: Ludwig-Maximilians-Universität München

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Innate immune responses are linked to key metabolic pathways, yet the proximal signaling events that connect these systems remain poorly understood. Here we show that phosphofructokinase 1, liver type (PFKL), a rate-limiting enzyme of glycolysis, is phosphorylated at Ser775 in macrophages following several innate stimuli. This phosphorylation increases the catalytic activity of PFKL, as shown by biochemical assays and glycolysis monitoring in cells expressing phosphorylation-defective PFKL variants. Using a genetic mouse model in which PFKL Ser775 phosphorylation cannot take place, we observe that upon activation, glycolysis in macrophages is lower than in the same cell population of wild-type animals. Consistent with their higher glycolytic activity, wild-type cells have higher levels of HIF1α and IL-1β than PfklS775A/S775A after LPS treatment. In an in vivo inflammation model, PfklS775A/S775A mice show reduced levels of MCP-1 and IL-1β. Our study thus identifies a molecular link between innate immune activation and early induction of glycolysis.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-50104-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50104-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-50104-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().