| First Author | Korotkevich E | Year | 2025 |
| Journal | Nat Commun | Volume | 16 |
| Issue | 1 | Pages | 5435 |
| PubMed ID | 40595506 | Mgi Jnum | J:369478 |
| Mgi Id | MGI:8218891 | Doi | 10.1038/s41467-025-60477-y |
| Citation | Korotkevich E, et al. (2025) Selfish mutations promote age-associated erosion of mtDNA integrity in mammals. Nat Commun 16(1):5435 |
| abstractText | Mutations in mitochondrial DNA (mtDNA) accumulate during aging and contribute to age-related conditions. High mtDNA copy number masks newly emerged recessive mutations; however, phenotypes develop when cellular levels of a mutant mtDNA rise above a critical threshold. The process driving this increase is unknown. Single-cell DNA sequencing of mouse and human hepatocytes detected increases in abundance of mutant alleles in sequences governing mtDNA replication. These alleles provided a replication advantage (drive) leading to accumulation of the affected genome along with a wide variety of associated passenger mutations, some of which are detrimental. The most prevalent human mtDNA disease variant, the 3243A>G allele, behaved as a driver, suggesting that drive underlies prevalence. We conclude that replicative drive amplifies linked mtDNA mutations to a threshold at which phenotypes are seen thereby promoting age-associated erosion of the mtDNA and influencing the transmission and progression of mitochondrial diseases. |
