Endothelial nitric oxide signaling in cellular and systemic metabolism.
6 affiliations
- 1Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt am Main, Germany; CardioPulmonary Institute, Frankfurt am Main, Germany. Electronic address: [email protected].
- 2Department of Physiology, Tulane University School of Medicine, New Orleans, USA. Electronic address: [email protected].
- 3Heinrich Heine University, Faculty of Mathematics and Natural Sciences, Institute of Metabolic Physiology, Düsseldorf, Germany; German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
- 4Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt am Main, Germany; CardioPulmonary Institute, Frankfurt am Main, Germany; German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany.
- 5Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, USA; Department of Molecular Physiology and Biophysics, University of Virginia School of Medicine, Charlottesville, USA.
- 6Department of Pharmacology, Pharmacotherapy and Clinical Pharmacy, Institute of Pharmacy, Life Science Faculty, Eberhard Karls University of Tübingen, Tübingen, Germany.
Abstract
Endothelial cell-derived nitric oxide (NO) is best known for its role in the regulation of vascular tone. However, growing evidence shows that endothelial NO acts as a flux- and compartment-dependent redox regulator of cellular and systemic metabolism. NO directly modulates metabolic networks through reversible or irreversible chemical modification of iron centers, reactive cysteine and tyrosine residues as well as fatty acids. Mechanisms of NO-mediated regulation of cellular metabolism include the S-nitrosation of enzymes involved in glycolysis, oxidative phosphorylation and nucleotide biosynthesis as well as the control of iron and heme availability. NO-derived nitrating species additionally generate electrophilic nitro-fatty acids, which act on metabolic and redox transcriptional programs through reversible cysteine adduction. Moreover, specialized endothelial cells contribute to metabolic regulation across organs, for example lipid trafficking in adipose tissue, iron homeostasis in the liver and erythropoiesis in the bone marrow. Finally, tissue/organ-specific endothelial dysfunction may disrupt organ and systemic metabolic control through multiple mechanisms, raising new questions and therapeutic opportunities. Understanding how cell- and enzymatic source-specific NO signaling defines endothelial heterogeneity and function may provide a mechanistic framework to address organ-specific endothelial dysfunction in cardiometabolic disease.
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BibTeX
@article{siragusa2026endothelial,
title = {{Endothelial nitric oxide signaling in cellular and systemic metabolism.}},
author = {Mauro Siragusa and Luke S Dunaway and Eckhard Lammert and Ingrid Fleming and Brant E Isakson and Miriam M Cortese-Krott},
journal = {Redox biology},
year = {2026},
month = oct,
doi = {10.1016/j.redox.2026.104443},
url = {https://europepmc.org/article/MED/42900998},
note = {CC BY},
}
RIS
TY - JOUR
TI - Endothelial nitric oxide signaling in cellular and systemic metabolism.
AU - Mauro Siragusa
AU - Luke S Dunaway
AU - Eckhard Lammert
AU - Ingrid Fleming
AU - Brant E Isakson
AU - Miriam M Cortese-Krott
PY - 2026
DA - 2026/10/18
JO - Redox biology
DO - 10.1016/j.redox.2026.104443
UR - https://europepmc.org/article/MED/42900998
AB - Endothelial cell-derived nitric oxide (NO) is best known for its role in the regulation of vascular tone. However, growing evidence shows that endothelial NO acts as a flux- and compartment-dependent redox regulator of cellular and systemic metabolism. NO directly modulates metabolic networks through reversible or irreversible chemical modification of iron centers, reactive cysteine and tyrosine residues as well as fatty acids. Mechanisms of NO-mediated regulation of cellular metabolism include the S-nitrosation of enzymes involved in glycolysis, oxidative phosphorylation and nucleotide biosynthesis as well as the control of iron and heme availability. NO-derived nitrating species additionally generate electrophilic nitro-fatty acids, which act on metabolic and redox transcriptional programs through reversible cysteine adduction. Moreover, specialized endothelial cells contribute to metabolic regulation across organs, for example lipid trafficking in adipose tissue, iron homeostasis in the liver and erythropoiesis in the bone marrow. Finally, tissue/organ-specific endothelial dysfunction may disrupt organ and systemic metabolic control through multiple mechanisms, raising new questions and therapeutic opportunities. Understanding how cell- and enzymatic source-specific NO signaling defines endothelial heterogeneity and function may provide a mechanistic framework to address organ-specific endothelial dysfunction in cardiometabolic disease.
SN - 2213-2317
ER -