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  PHD2 is a regulator for glycolytic reprogramming in macrophages.

Guentsch, A., Beneke, A., Swain, L., Farhat, K., Nagarajan, S., Wielockx, B., et al. (2017). PHD2 is a regulator for glycolytic reprogramming in macrophages. Molecular and Cellular Biology, 37(1): e00236-16. doi:10.1128/MCB.00236-16.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-304A-4 Version Permalink: http://hdl.handle.net/21.11116/0000-0001-240A-C
Genre: Journal Article

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 Creators:
Guentsch, A., Author
Beneke, A., Author
Swain, L., Author
Farhat, K., Author
Nagarajan, S., Author
Wielockx, B., Author
Raithatha, K., Author
Dudek, J., Author
Rehling, P.1, Author              
Zieseniss, A., Author
Jatho, A., Author
Chong, M., Author
Santos, C. X. C., Author
Shah, A. M., Author
Katschinski, D. M., Author
Affiliations:
1Max Planck Fellow Peter Rehling, ou_1298545              

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Free keywords: PDK; prolyl-4-hydroxylase domain; dioxygenases; hypoxia; macrophages
 Abstract: The prolyl-4-hydroxylase domain (PHD) enzymes are regarded as the molecular oxygen sensors. There is an interplay between oxygen availability and cellular metabolism, which in turn has significant effects on the functionality of innate immune cells, such as macrophages. However, if and how PHD enzymes affect macrophage metabolism are enigmatic. We hypothesized that macrophage metabolism and function can be controlled via manipulation of PHD2. We characterized the metabolic phenotypes of PHD2-deficient RAW cells and primary PHD2 knockout bone marrow-derived macrophages (BMDM). Both showed typical features of anaerobic glycolysis, which were paralleled by increased pyruvate dehydrogenase kinase 1 (PDK1) protein levels and a decreased pyruvate dehydrogenase enzyme activity. Metabolic alterations were associated with an impaired cellular functionality. Inhibition of PDK1 or knockout of hypoxia-inducible factor 1 alpha (HIF-1 alpha) reversed the metabolic phenotype and impaired the functionality of the PHD2-deficient RAW cells and BMDM. Taking these results together, we identified a critical role of PHD2 for a reversible glycolytic reprogramming in macrophages with a direct impact on their function. We suggest that PHD2 serves as an adjustable switch to control macropha(g)e behavior.

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Language(s): eng - English
 Dates: 2017-01
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1128/MCB.00236-16
 Degree: -

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Title: Molecular and Cellular Biology
Source Genre: Journal
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Pages: 16 Volume / Issue: 37 (1) Sequence Number: e00236-16 Start / End Page: - Identifier: -