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Mitochondrial DNA copy number in human disease: the more the better?
Most of the genetic information has been lost or transferred to the nucleus during the evolution of mitochondria. Nevertheless, mitochondria have retained their own genome that is essential for oxidative phosphorylation (OXPHOS). In mammals, a gene‐dense circular mitochondrial DNA (mtDNA) of about 1...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247411/ https://www.ncbi.nlm.nih.gov/pubmed/33314045 http://dx.doi.org/10.1002/1873-3468.14021 |
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author | Filograna, Roberta Mennuni, Mara Alsina, David Larsson, Nils‐Göran |
author_facet | Filograna, Roberta Mennuni, Mara Alsina, David Larsson, Nils‐Göran |
author_sort | Filograna, Roberta |
collection | PubMed |
description | Most of the genetic information has been lost or transferred to the nucleus during the evolution of mitochondria. Nevertheless, mitochondria have retained their own genome that is essential for oxidative phosphorylation (OXPHOS). In mammals, a gene‐dense circular mitochondrial DNA (mtDNA) of about 16.5 kb encodes 13 proteins, which constitute only 1% of the mitochondrial proteome. Mammalian mtDNA is present in thousands of copies per cell and mutations often affect only a fraction of them. Most pathogenic human mtDNA mutations are recessive and only cause OXPHOS defects if present above a certain critical threshold. However, emerging evidence strongly suggests that the proportion of mutated mtDNA copies is not the only determinant of disease but that also the absolute copy number matters. In this review, we critically discuss current knowledge of the role of mtDNA copy number regulation in various types of human diseases, including mitochondrial disorders, neurodegenerative disorders and cancer, and during ageing. We also provide an overview of new exciting therapeutic strategies to directly manipulate mtDNA to restore OXPHOS in mitochondrial diseases. |
format | Online Article Text |
id | pubmed-8247411 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82474112021-07-02 Mitochondrial DNA copy number in human disease: the more the better? Filograna, Roberta Mennuni, Mara Alsina, David Larsson, Nils‐Göran FEBS Lett Review Articles Most of the genetic information has been lost or transferred to the nucleus during the evolution of mitochondria. Nevertheless, mitochondria have retained their own genome that is essential for oxidative phosphorylation (OXPHOS). In mammals, a gene‐dense circular mitochondrial DNA (mtDNA) of about 16.5 kb encodes 13 proteins, which constitute only 1% of the mitochondrial proteome. Mammalian mtDNA is present in thousands of copies per cell and mutations often affect only a fraction of them. Most pathogenic human mtDNA mutations are recessive and only cause OXPHOS defects if present above a certain critical threshold. However, emerging evidence strongly suggests that the proportion of mutated mtDNA copies is not the only determinant of disease but that also the absolute copy number matters. In this review, we critically discuss current knowledge of the role of mtDNA copy number regulation in various types of human diseases, including mitochondrial disorders, neurodegenerative disorders and cancer, and during ageing. We also provide an overview of new exciting therapeutic strategies to directly manipulate mtDNA to restore OXPHOS in mitochondrial diseases. John Wiley and Sons Inc. 2020-12-25 2021-04 /pmc/articles/PMC8247411/ /pubmed/33314045 http://dx.doi.org/10.1002/1873-3468.14021 Text en © 2020 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Review Articles Filograna, Roberta Mennuni, Mara Alsina, David Larsson, Nils‐Göran Mitochondrial DNA copy number in human disease: the more the better? |
title | Mitochondrial DNA copy number in human disease: the more the better? |
title_full | Mitochondrial DNA copy number in human disease: the more the better? |
title_fullStr | Mitochondrial DNA copy number in human disease: the more the better? |
title_full_unstemmed | Mitochondrial DNA copy number in human disease: the more the better? |
title_short | Mitochondrial DNA copy number in human disease: the more the better? |
title_sort | mitochondrial dna copy number in human disease: the more the better? |
topic | Review Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247411/ https://www.ncbi.nlm.nih.gov/pubmed/33314045 http://dx.doi.org/10.1002/1873-3468.14021 |
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