Tyrosine nitration: An emerging mechanistic landscape in neurodegeneration and cardiopulmonary disease.
5 affiliations
- 1Center for Translational Science, Florida International University, Port St. Lucie, Florida, 34987, USA; Department of Cellular & Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, Port St. Lucie, Florida, 34987, USA.
- 2Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR, 97331, USA.
- 3Department of Neurology, Emory University School of Medicine, Atlanta, GA, 30322, USA; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, 30322, USA.
- 4Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR, 97331, USA; Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331, USA.
- 5Center for Translational Science, Florida International University, Port St. Lucie, Florida, 34987, USA; Department of Cellular & Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, Port St. Lucie, Florida, 34987, USA. Electronic address: [email protected].
Abstract
Protein tyrosine nitration is a post-translational modification associated with conditions of oxidative and inflammatory stress, driven by the production of reactive oxygen and nitrogen species (ROS and RNS). Once considered primarily a footprint of oxidative damage, tyrosine nitration is increasingly recognized as a selective modification that, in specific biological contexts, can alter protein structure, stability, enzymatic activity, and interaction networks. Mechanistically, nitration occurs through peroxynitrite-dependent and heme-peroxidase-dependent pathways and preferentially targets specific tyrosine residues based on local protein structure, solvent accessibility, and microenvironmental chemistry. Accumulating evidence has identified disease-specific nitration signatures across multiple pathological contexts. In neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, nitration of proteins such as tau, α-synuclein, manganese superoxide dismutase, ATP synthase, glyceraldehyde-3-phosphate dehydrogenase, heat shock proteins, and cytoskeletal components contributes to mitochondrial dysfunction, protein aggregation, metabolic failure, and neuronal loss. Similarly, in cardiovascular and pulmonary diseases, protein tyrosine nitration disrupts vascular and epithelial homeostasis by impairing endothelial signaling, fibrinolysis, lipid metabolism, and barrier integrity through modification of key regulatory proteins. By influencing phosphorylation-dependent signaling, enzymatic function, and protein-protein interactions, tyrosine nitration contributes to the connection between redox imbalance and progressive cellular and tissue dysfunction. This review summarizes current mechanistic insights into site-specific protein tyrosine nitration, highlights the emerging disease-associated nitroproteome, and discusses how advances in analytical and structural approaches are redefining nitration as a functional regulatory modification. Understanding the molecular determinants and consequences of tyrosine nitration may enable the development of targeted diagnostics and therapeutic strategies across diverse human diseases.
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BibTeX
@article{adrita2026tyrosine,
title = {{Tyrosine nitration: An emerging mechanistic landscape in neurodegeneration and cardiopulmonary disease.}},
author = {Nirbachita Adrita and Inge Claassen and Miranda Huerta and Stephen M Black and Alvaro G Estevez and Blaine R Roberts and Joseph S Beckman and Maria Clara Franco},
journal = {Redox biology},
year = {2026},
month = oct,
doi = {10.1016/j.redox.2026.104423},
url = {https://europepmc.org/article/MED/42843275},
note = {CC BY},
}
RIS
TY - JOUR
TI - Tyrosine nitration: An emerging mechanistic landscape in neurodegeneration and cardiopulmonary disease.
AU - Nirbachita Adrita
AU - Inge Claassen
AU - Miranda Huerta
AU - Stephen M Black
AU - Alvaro G Estevez
AU - Blaine R Roberts
AU - Joseph S Beckman
AU - Maria Clara Franco
PY - 2026
DA - 2026/10/03
JO - Redox biology
DO - 10.1016/j.redox.2026.104423
UR - https://europepmc.org/article/MED/42843275
AB - Protein tyrosine nitration is a post-translational modification associated with conditions of oxidative and inflammatory stress, driven by the production of reactive oxygen and nitrogen species (ROS and RNS). Once considered primarily a footprint of oxidative damage, tyrosine nitration is increasingly recognized as a selective modification that, in specific biological contexts, can alter protein structure, stability, enzymatic activity, and interaction networks. Mechanistically, nitration occurs through peroxynitrite-dependent and heme-peroxidase-dependent pathways and preferentially targets specific tyrosine residues based on local protein structure, solvent accessibility, and microenvironmental chemistry. Accumulating evidence has identified disease-specific nitration signatures across multiple pathological contexts. In neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, nitration of proteins such as tau, α-synuclein, manganese superoxide dismutase, ATP synthase, glyceraldehyde-3-phosphate dehydrogenase, heat shock proteins, and cytoskeletal components contributes to mitochondrial dysfunction, protein aggregation, metabolic failure, and neuronal loss. Similarly, in cardiovascular and pulmonary diseases, protein tyrosine nitration disrupts vascular and epithelial homeostasis by impairing endothelial signaling, fibrinolysis, lipid metabolism, and barrier integrity through modification of key regulatory proteins. By influencing phosphorylation-dependent signaling, enzymatic function, and protein-protein interactions, tyrosine nitration contributes to the connection between redox imbalance and progressive cellular and tissue dysfunction. This review summarizes current mechanistic insights into site-specific protein tyrosine nitration, highlights the emerging disease-associated nitroproteome, and discusses how advances in analytical and structural approaches are redefining nitration as a functional regulatory modification. Understanding the molecular determinants and consequences of tyrosine nitration may enable the development of targeted diagnostics and therapeutic strategies across diverse human diseases.
SN - 2213-2317
ER -