Mitochondrial tRNA leucine 1 (UUR) with m.3243A>G mutation

The m.3243A>G mutation refers to an adenine-to-guanine transition at position 3243 in human mitochondrial DNA, within the MT-TL1 gene encoding mitochondrial tRNA leucine 1 (UUR)[1][3][5]. It is the most common pathogenic point mutation in mitochondrial DNA and leads to impaired mitochondrial translation, defective protein synthesis for components of the respiratory chain, and ultimately, dysfunctional oxidative phosphorylation. Clinically, it is associated with a wide spectrum of diseases, most notably MELAS syndrome, maternally inherited diabetes and deafness (MIDD), neuromuscular, cardiac, and renal phenotypes[1][3][5][7]. The clinical severity depends on tissue distribution and the proportion (heteroplasmy) of mutant mtDNA molecules. The m.3243A>G mutation is used as a biomarker for diagnosing mitochondrial DNA-related disorders and may influence cancer response to immunotherapies[2][4][8]. No current pharmacological treatments directly correct this mutation, though novel mtDNA-targeting therapies are in preclinical and early clinical development[4][6][8].

Other names

mtDNA with m.3243A>G mutationm.3243A>G mutationMT-TL1 m.3243A>G3243A>G mutationMELAS mutation (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes)

Targeting cells harboring the mutation for immunotherapy sensitization[2] - Direct or indirect induction of mitochondrial dysfunction in targeted cancer therapy[4][6][8]