线粒体DNA
生物
人类线粒体遗传学
线粒体
遗传学
粒线体疾病
基因组
氧化磷酸化
基因
DNA
生物化学
作者
Roberta Filograna,Mara Mennuni,David Alsina,Nils‐Göran Larsson
出处
期刊:FEBS Letters
[Wiley]
日期:2020-12-25
卷期号:595 (8): 976-1002
被引量:271
标识
DOI:10.1002/1873-3468.14021
摘要
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.
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