Selfish mutations promote age-associated erosion of mtDNA integrity in mammals.

ABSTRACT: 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 concl

SUBMITTER: Korotkevich E 

PROVIDER: S-EPMC12216451 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature