Advances in Biology & Earth Sciences

Mitochondrial DNA (mtDNA) is highly susceptible to mutations that disrupt oxidative phosphorylation and contribute to human diseases. Among the protein-coding and tRNA genes, ND1, ATP6 and tRNALeu(UUR) have been identified as major mutational hotspots. This study provides an updated overview of these mutations using MITOMAP 2023 and evaluates their clinical correlations. Data analysis revealed that ND1 and ATP6 harbor a high density of missense mutations, many of which are strongly associated with Leber’s Hereditary Optic Neuropathy (LHON), while mutations in tRNALeu(UUR) are predominantly linked to maternally inherited diabetes and deafness (MIDD). Comparative analysis with earlier datasets confirmed a consistent enrichment of pathogenic variants in these loci, highlighting their critical role in mitochondrial dysfunction. Mutations in ND1 and ATP6 mainly impair electron transfer within the respiratory chain, whereas tRNALeu(UUR) mutations disrupt mitochondrial protein synthesis, both leading to increased oxidative stress and metabolic imbalance. These findings reinforce the importance of ND1, ATP6 and tRNALeu(UUR) as key targets in mitochondrial disease research and suggest that the integration of updated genomic databases can enhance genotype-guided diagnostics and therapeutic strategies.