Language:

Nitric oxide orchestrates metabolic rewiring in M1 macrophages by targeting aconitase 2 and pyruvate dehydrogenase

Nature communications, 2020-02, Vol.11 (1), p.698-17, Article 698 [Peer Reviewed Journal]

This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2020 ;ISSN: 2041-1723 ;EISSN: 2041-1723 ;DOI: 10.1038/s41467-020-14433-7 ;PMID: 32019928

Full text available

Citations Cited by

Actions
1. Add to My Research
2. Remove from My Research
3. E-mail
4. Print
5. Permalink
6. Citation
7. EasyBib
8. EndNote
9. RefWorks
10. Delicious
11. Export RIS
12. Export BibTeX

Title:
Nitric oxide orchestrates metabolic rewiring in M1 macrophages by targeting aconitase 2 and pyruvate dehydrogenase
Author: Palmieri, Erika M ; Gonzalez-Cotto, Marieli ; Baseler, Walter A ; Davies, Luke C ; Ghesquière, Bart ; Maio, Nunziata ; Rice, Christopher M ; Rouault, Tracey A ; Cassel, Teresa ; Higashi, Richard M ; Lane, Andrew N ; Fan, Teresa W-M ; Wink, David A ; McVicar, Daniel W
Subjects: Accumulation ; Aconitate Hydratase - genetics ; Aconitate Hydratase - metabolism ; Animals ; Cell activation ; Citric acid ; Citric Acid - metabolism ; Citric Acid Cycle ; Dehydrogenase ; Dehydrogenases ; Electron transport ; Electron transport chain ; Electron Transport Chain Complex Proteins - genetics ; Electron Transport Chain Complex Proteins - metabolism ; Glutamine ; Glycolysis ; Humans ; Hypoxia ; Hypoxia-Inducible Factor 1, alpha Subunit - genetics ; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism ; Hypoxia-inducible factor 1a ; Inflammation ; Inflammation - genetics ; Inflammation - metabolism ; Macrophages ; Macrophages - enzymology ; Macrophages - metabolism ; Metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria ; Mitochondria - enzymology ; Mitochondria - metabolism ; Nitric oxide ; Nitric Oxide - metabolism ; Nitric Oxide Synthase Type II - genetics ; Nitric Oxide Synthase Type II - metabolism ; Phenotypes ; Polarization ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase - genetics ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase - metabolism ; Pyruvic acid ; Pyruvic Acid - metabolism ; Rewiring ; Tricarboxylic acid cycle
Is Part Of: Nature communications, 2020-02, Vol.11 (1), p.698-17, Article 698
Description: Profound metabolic changes are characteristic of macrophages during classical activation and have been implicated in this phenotype. Here we demonstrate that nitric oxide (NO) produced by murine macrophages is responsible for TCA cycle alterations and citrate accumulation associated with polarization. C tracing and mitochondrial respiration experiments map NO-mediated suppression of metabolism to mitochondrial aconitase (ACO2). Moreover, we find that inflammatory macrophages reroute pyruvate away from pyruvate dehydrogenase (PDH) in an NO-dependent and hypoxia-inducible factor 1α (Hif1α)-independent manner, thereby promoting glutamine-based anaplerosis. Ultimately, NO accumulation leads to suppression and loss of mitochondrial electron transport chain (ETC) complexes. Our data reveal that macrophages metabolic rewiring, in vitro and in vivo, is dependent on NO targeting specific pathways, resulting in reduced production of inflammatory mediators. Our findings require modification to current models of macrophage biology and demonstrate that reprogramming of metabolism should be considered a result rather than a mediator of inflammatory polarization.
Publisher: England: Nature Publishing Group
Language: English
Identifier: ISSN: 2041-1723
EISSN: 2041-1723
DOI: 10.1038/s41467-020-14433-7
PMID: 32019928
Source: MEDLINE
PubMed Central
ProQuest Central
DOAJ Directory of Open Access Journals

Back to results list


INSPIRE LIBRARY - TON DUC THANG UNIVERSITY	(84-028) 37 755 057	Feedback
19 Nguyen Huu Tho St. Dist.7, HCM	thuvien@tdtu.edu.vn	Feedback

Nitric oxide orchestrates metabolic rewiring in M1 macrophages by targeting aconitase 2 and pyruvate dehydrogenase

Searching Remote Databases, Please Wait