Mitochondrial DNA carrying the m.3243A>G mutation (tRNA Leu(UUR) gene) (m.3243A>G mutant mtDNA (Note: "m.3243G" is sometimes used informally to refer to the mutant allele but canonical abbreviation is usually "m.3243A>G"))

The m.3243A>G mutation is one of the most common pathogenic mitochondrial DNA mutations, located in the gene encoding the mitochondrial tRNA leucine (UUR). Present in hundreds to thousands of copies within mitochondria, the proportion of mutant to wild-type genomes (heteroplasmy) greatly influences disease severity and tissue involvement. Low heteroplasmy (~10–30%) can manifest as diabetes and hearing loss; higher levels (~50–90%) are linked to severe neurological diseases, such as MELAS. The mutation impairs correct tRNA modification and mitochondrial protein synthesis, resulting in defective respiration, increased glycolysis, and energy deficiency in affected tissues. It plays a direct role in several mitochondrial syndromes, particularly MELAS, and is a target for gene-editing therapeutic strategies like mitoARCUS, which aim to selectively eliminate the mutant genomes to restore normal mitochondrial function

Other names

m.3243A>G mutationMELAS-associated mtDNA mutationtRNA Leu(UUR) m.3243A>G mutantMELAS mutation

Selective cleavage and elimination of mutant mtDNA (by engineered nucleases such as mitoARCUS) Not applicable for standard drugs (mutation not a receptor/enzyme)