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Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System

Nearly half a century has passed since the discovery of cytoplasmic inheritance of human chloramphenicol resistance. The inheritance was then revealed to take place maternally by mitochondrial DNA (mtDNA). Later, a number of mutations in mtDNA were identified as a cause of severe inheritable metabol...

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Autores principales: Tanaka, Masaru, Szabó, Ágnes, Spekker, Eleonóra, Polyák, Helga, Tóth, Fanni, Vécsei, László
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9406499/
https://www.ncbi.nlm.nih.gov/pubmed/36010683
http://dx.doi.org/10.3390/cells11162607
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author Tanaka, Masaru
Szabó, Ágnes
Spekker, Eleonóra
Polyák, Helga
Tóth, Fanni
Vécsei, László
author_facet Tanaka, Masaru
Szabó, Ágnes
Spekker, Eleonóra
Polyák, Helga
Tóth, Fanni
Vécsei, László
author_sort Tanaka, Masaru
collection PubMed
description Nearly half a century has passed since the discovery of cytoplasmic inheritance of human chloramphenicol resistance. The inheritance was then revealed to take place maternally by mitochondrial DNA (mtDNA). Later, a number of mutations in mtDNA were identified as a cause of severe inheritable metabolic diseases with neurological manifestation, and the impairment of mitochondrial functions has been probed in the pathogenesis of a wide range of illnesses including neurodegenerative diseases. Recently, a growing number of preclinical studies have revealed that animal behaviors are influenced by the impairment of mitochondrial functions and possibly by the loss of mitochondrial stress resilience. Indeed, as high as 54% of patients with one of the most common primary mitochondrial diseases, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, present psychiatric symptoms including cognitive impairment, mood disorder, anxiety, and psychosis. Mitochondria are multifunctional organelles which produce cellular energy and play a major role in other cellular functions including homeostasis, cellular signaling, and gene expression, among others. Mitochondrial functions are observed to be compromised and to become less resilient under continuous stress. Meanwhile, stress and inflammation have been linked to the activation of the tryptophan (Trp)–kynurenine (KYN) metabolic system, which observably contributes to the development of pathological conditions including neurological and psychiatric disorders. This review discusses the functions of mitochondria and the Trp-KYN system, the interaction of the Trp-KYN system with mitochondria, and the current understanding of the involvement of mitochondria and the Trp-KYN system in preclinical and clinical studies of major neurological and psychiatric diseases.
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spelling pubmed-94064992022-08-26 Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System Tanaka, Masaru Szabó, Ágnes Spekker, Eleonóra Polyák, Helga Tóth, Fanni Vécsei, László Cells Review Nearly half a century has passed since the discovery of cytoplasmic inheritance of human chloramphenicol resistance. The inheritance was then revealed to take place maternally by mitochondrial DNA (mtDNA). Later, a number of mutations in mtDNA were identified as a cause of severe inheritable metabolic diseases with neurological manifestation, and the impairment of mitochondrial functions has been probed in the pathogenesis of a wide range of illnesses including neurodegenerative diseases. Recently, a growing number of preclinical studies have revealed that animal behaviors are influenced by the impairment of mitochondrial functions and possibly by the loss of mitochondrial stress resilience. Indeed, as high as 54% of patients with one of the most common primary mitochondrial diseases, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, present psychiatric symptoms including cognitive impairment, mood disorder, anxiety, and psychosis. Mitochondria are multifunctional organelles which produce cellular energy and play a major role in other cellular functions including homeostasis, cellular signaling, and gene expression, among others. Mitochondrial functions are observed to be compromised and to become less resilient under continuous stress. Meanwhile, stress and inflammation have been linked to the activation of the tryptophan (Trp)–kynurenine (KYN) metabolic system, which observably contributes to the development of pathological conditions including neurological and psychiatric disorders. This review discusses the functions of mitochondria and the Trp-KYN system, the interaction of the Trp-KYN system with mitochondria, and the current understanding of the involvement of mitochondria and the Trp-KYN system in preclinical and clinical studies of major neurological and psychiatric diseases. MDPI 2022-08-21 /pmc/articles/PMC9406499/ /pubmed/36010683 http://dx.doi.org/10.3390/cells11162607 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Tanaka, Masaru
Szabó, Ágnes
Spekker, Eleonóra
Polyák, Helga
Tóth, Fanni
Vécsei, László
Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System
title Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System
title_full Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System
title_fullStr Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System
title_full_unstemmed Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System
title_short Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System
title_sort mitochondrial impairment: a common motif in neuropsychiatric presentation? the link to the tryptophan–kynurenine metabolic system
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9406499/
https://www.ncbi.nlm.nih.gov/pubmed/36010683
http://dx.doi.org/10.3390/cells11162607
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