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Nitric Oxide Deficiency in Mitochondrial Disorders: The Utility of Arginine and Citrulline

Mitochondrial diseases represent a growing list of clinically heterogeneous disorders that are associated with dysfunctional mitochondria and multisystemic manifestations. In spite of a better understanding of the underlying pathophysiological basis of mitochondrial disorders, treatment options rema...

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Autores principales: Almannai, Mohammed, El-Hattab, Ayman W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374159/
https://www.ncbi.nlm.nih.gov/pubmed/34421535
http://dx.doi.org/10.3389/fnmol.2021.682780
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author Almannai, Mohammed
El-Hattab, Ayman W.
author_facet Almannai, Mohammed
El-Hattab, Ayman W.
author_sort Almannai, Mohammed
collection PubMed
description Mitochondrial diseases represent a growing list of clinically heterogeneous disorders that are associated with dysfunctional mitochondria and multisystemic manifestations. In spite of a better understanding of the underlying pathophysiological basis of mitochondrial disorders, treatment options remain limited. Over the past two decades, there is growing evidence that patients with mitochondrial disorders have nitric oxide (NO) deficiency due to the limited availability of NO substrates, arginine and citrulline; decreased activity of nitric oxide synthase (NOS); and NO sequestration. Studies evaluating the use of arginine in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) presenting with stroke-like episodes showed symptomatic improvement after acute administration as well as a reduction in the frequency and severity of stroke-like episodes following chronic use. Citrulline, another NO precursor, was shown through stable isotope studies to result in a greater increase in NO synthesis. Recent studies showed a positive response of arginine and citrulline in other mitochondrial disorders besides MELAS. Randomized-controlled studies with a larger number of patients are warranted to better understand the role of NO deficiency in mitochondrial disorders and the efficacy of NO precursors as treatment modalities in these disorders.
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spelling pubmed-83741592021-08-20 Nitric Oxide Deficiency in Mitochondrial Disorders: The Utility of Arginine and Citrulline Almannai, Mohammed El-Hattab, Ayman W. Front Mol Neurosci Molecular Neuroscience Mitochondrial diseases represent a growing list of clinically heterogeneous disorders that are associated with dysfunctional mitochondria and multisystemic manifestations. In spite of a better understanding of the underlying pathophysiological basis of mitochondrial disorders, treatment options remain limited. Over the past two decades, there is growing evidence that patients with mitochondrial disorders have nitric oxide (NO) deficiency due to the limited availability of NO substrates, arginine and citrulline; decreased activity of nitric oxide synthase (NOS); and NO sequestration. Studies evaluating the use of arginine in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) presenting with stroke-like episodes showed symptomatic improvement after acute administration as well as a reduction in the frequency and severity of stroke-like episodes following chronic use. Citrulline, another NO precursor, was shown through stable isotope studies to result in a greater increase in NO synthesis. Recent studies showed a positive response of arginine and citrulline in other mitochondrial disorders besides MELAS. Randomized-controlled studies with a larger number of patients are warranted to better understand the role of NO deficiency in mitochondrial disorders and the efficacy of NO precursors as treatment modalities in these disorders. Frontiers Media S.A. 2021-08-05 /pmc/articles/PMC8374159/ /pubmed/34421535 http://dx.doi.org/10.3389/fnmol.2021.682780 Text en Copyright © 2021 Almannai and El-Hattab. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Neuroscience
Almannai, Mohammed
El-Hattab, Ayman W.
Nitric Oxide Deficiency in Mitochondrial Disorders: The Utility of Arginine and Citrulline
title Nitric Oxide Deficiency in Mitochondrial Disorders: The Utility of Arginine and Citrulline
title_full Nitric Oxide Deficiency in Mitochondrial Disorders: The Utility of Arginine and Citrulline
title_fullStr Nitric Oxide Deficiency in Mitochondrial Disorders: The Utility of Arginine and Citrulline
title_full_unstemmed Nitric Oxide Deficiency in Mitochondrial Disorders: The Utility of Arginine and Citrulline
title_short Nitric Oxide Deficiency in Mitochondrial Disorders: The Utility of Arginine and Citrulline
title_sort nitric oxide deficiency in mitochondrial disorders: the utility of arginine and citrulline
topic Molecular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374159/
https://www.ncbi.nlm.nih.gov/pubmed/34421535
http://dx.doi.org/10.3389/fnmol.2021.682780
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