Mitochondrial DNA copy number in human disease: the more the better?
| Autor: | Nils-Göran Larsson, David Alsina, Roberta Filograna, Mara Mennuni |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Mitochondrial DNA
DNA Copy Number Variations mtDNA copy number Mitochondrial disease Cell Biophysics Review Article Disease Oxidative phosphorylation Mitochondrion Biology DNA Mitochondrial Biochemistry Genome 03 medical and health sciences Structural Biology Neoplasms Genetics medicine Animals Humans cancer Review Articles Molecular Biology TFAM 030304 developmental biology Molecular Basis of Disease mitochondrial diseases 0303 health sciences mtDNA 030302 biochemistry & molecular biology Neurodegenerative Diseases DNA Neoplasm Cell Biology medicine.disease Mitochondria 3. Good health medicine.anatomical_structure ageing neurodegenerative disorders Parkinson’s disease Alzheimer’s disease |
| Zdroj: | Febs Letters |
| ISSN: | 1873-3468 0014-5793 |
| DOI: | 10.1002/1873-3468.14021 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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