Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Filograna, Roberta, Mennuni, Mara, Alsina, David, Larsson, Nils‐Göran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
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
_version_ 1783716518909968384
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
work_keys_str_mv AT filogranaroberta mitochondrialdnacopynumberinhumandiseasethemorethebetter
AT mennunimara mitochondrialdnacopynumberinhumandiseasethemorethebetter
AT alsinadavid mitochondrialdnacopynumberinhumandiseasethemorethebetter
AT larssonnilsgoran mitochondrialdnacopynumberinhumandiseasethemorethebetter