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The molecular pathology of pathogenic mitochondrial tRNA variants
Mitochondrial diseases are clinically and genetically heterogeneous disorders, caused by pathogenic variants in either the nuclear or mitochondrial genome. This heterogeneity is particularly striking for disease caused by variants in mitochondrial DNA‐encoded tRNA (mt‐tRNA) genes, posing challenges...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600956/ https://www.ncbi.nlm.nih.gov/pubmed/33513266 http://dx.doi.org/10.1002/1873-3468.14049 |
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author | Richter, Uwe McFarland, Robert Taylor, Robert W. Pickett, Sarah J. |
author_facet | Richter, Uwe McFarland, Robert Taylor, Robert W. Pickett, Sarah J. |
author_sort | Richter, Uwe |
collection | PubMed |
description | Mitochondrial diseases are clinically and genetically heterogeneous disorders, caused by pathogenic variants in either the nuclear or mitochondrial genome. This heterogeneity is particularly striking for disease caused by variants in mitochondrial DNA‐encoded tRNA (mt‐tRNA) genes, posing challenges for both the treatment of patients and understanding the molecular pathology. In this review, we consider disease caused by the two most common pathogenic mt‐tRNA variants: m.3243A>G (within MT‐TL1, encoding mt‐tRNA(Leu(UUR))) and m.8344A>G (within MT‐TK, encoding mt‐tRNA(Lys)), which together account for the vast majority of all mt‐tRNA‐related disease. We compare and contrast the clinical disease they are associated with, as well as their molecular pathologies, and consider what is known about the likely molecular mechanisms of disease. Finally, we discuss the role of mitochondrial–nuclear crosstalk in the manifestation of mt‐tRNA‐associated disease and how research in this area not only has the potential to uncover molecular mechanisms responsible for the vast clinical heterogeneity associated with these variants but also pave the way to develop treatment options for these devastating diseases. |
format | Online Article Text |
id | pubmed-8600956 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86009562021-11-23 The molecular pathology of pathogenic mitochondrial tRNA variants Richter, Uwe McFarland, Robert Taylor, Robert W. Pickett, Sarah J. FEBS Lett Review Articles Mitochondrial diseases are clinically and genetically heterogeneous disorders, caused by pathogenic variants in either the nuclear or mitochondrial genome. This heterogeneity is particularly striking for disease caused by variants in mitochondrial DNA‐encoded tRNA (mt‐tRNA) genes, posing challenges for both the treatment of patients and understanding the molecular pathology. In this review, we consider disease caused by the two most common pathogenic mt‐tRNA variants: m.3243A>G (within MT‐TL1, encoding mt‐tRNA(Leu(UUR))) and m.8344A>G (within MT‐TK, encoding mt‐tRNA(Lys)), which together account for the vast majority of all mt‐tRNA‐related disease. We compare and contrast the clinical disease they are associated with, as well as their molecular pathologies, and consider what is known about the likely molecular mechanisms of disease. Finally, we discuss the role of mitochondrial–nuclear crosstalk in the manifestation of mt‐tRNA‐associated disease and how research in this area not only has the potential to uncover molecular mechanisms responsible for the vast clinical heterogeneity associated with these variants but also pave the way to develop treatment options for these devastating diseases. John Wiley and Sons Inc. 2021-02-12 2021-04 /pmc/articles/PMC8600956/ /pubmed/33513266 http://dx.doi.org/10.1002/1873-3468.14049 Text en © 2021 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Articles Richter, Uwe McFarland, Robert Taylor, Robert W. Pickett, Sarah J. The molecular pathology of pathogenic mitochondrial tRNA variants |
title | The molecular pathology of pathogenic mitochondrial tRNA variants |
title_full | The molecular pathology of pathogenic mitochondrial tRNA variants |
title_fullStr | The molecular pathology of pathogenic mitochondrial tRNA variants |
title_full_unstemmed | The molecular pathology of pathogenic mitochondrial tRNA variants |
title_short | The molecular pathology of pathogenic mitochondrial tRNA variants |
title_sort | molecular pathology of pathogenic mitochondrial trna variants |
topic | Review Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600956/ https://www.ncbi.nlm.nih.gov/pubmed/33513266 http://dx.doi.org/10.1002/1873-3468.14049 |
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