ORCID: https://orcid.org/0000-0002-8197-9374; Masgrau-Alsina, Sergi; Kamper, Julia M. ORCID: https://orcid.org/0000-0002-3801-864X; Henne, Antonia ORCID: https://orcid.org/0000-0001-6870-5312; Heinz, Alexander; Berouti, Marleen; Schmacke, Niklas A. ORCID: https://orcid.org/0000-0002-3998-1139; Hiller, Karsten ORCID: https://orcid.org/0000-0001-9322-5820; Kremmer, Elisabeth; Wefers, Benedikt ORCID: https://orcid.org/0000-0002-2492-9389; Wurst, Wolfgang ORCID: https://orcid.org/0000-0003-4422-7410; Sperandio, Markus ORCID: https://orcid.org/0000-0002-7689-3613; Ruland, Jürgen ORCID: https://orcid.org/0000-0002-8381-3597; Fröhlich, Thomas ORCID: https://orcid.org/0000-0002-4709-3211 und Hornung, Veit ORCID: https://orcid.org/0000-0002-4150-194X
(2024):
Phosphorylation of PFKL regulates metabolic reprogramming in macrophages following pattern recognition receptor activation.
In: Nature Communications, Vol. 15, 6438
[PDF, 2MB]
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.
| Item Type: | Journal article |
|---|---|
| Faculties: | Chemistry and Pharmacy > GeneCenter Biology > Department Biology II Medicine > Adolf Butenandt Institute Medicine > Institute of Cardiovascular Physiology and Pathophysiology Medicine > Munich Cluster for Systems Neurology (SyNergy) Medicine > Institute for Stroke and Dementia Research (ISD) |
| Subjects: | 600 Technology > 610 Medicine and health |
| URN: | urn:nbn:de:bvb:19-epub-122986-6 |
| ISSN: | 2041-1723 |
| Language: | English |
| Item ID: | 122986 |
| Date Deposited: | 11. Dec 2024 15:54 |
| Last Modified: | 11. Dec 2024 15:54 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198 |
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