Mitochondrial DNA copy number in human disease: the more the better?
FEBS Lett
; 595(8): 976-1002, 2021 04.
Article
in En
| MEDLINE
| ID: mdl-33314045
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA, Mitochondrial
/
DNA, Neoplasm
/
Neurodegenerative Diseases
/
Mitochondrial Diseases
/
DNA Copy Number Variations
/
Mitochondria
/
Neoplasms
Limits:
Animals
/
Humans
Language:
En
Journal:
FEBS Lett
Year:
2021
Document type:
Article
Affiliation country:
Suecia