In this report, we investigated the pathogenic mechanism underlying the
deafness-associated mitochondrial(mt)
tRNAAsp 7551A > G mutation. The m.7551A > G mutation is localized at a highly conserved
nucleotide(A37), adjacent (3') to the
anticodon, which is important for the fidelity of
codon recognition and stabilization in functional tRNAs. It was anticipated that the m.7551A > G mutation altered the structure and function of mt-
tRNAAsp The primer extension assay demonstrated that the m.7551A > G mutation created the m1G37 modification of mt-
tRNAAsp Using cybrid cell lines generated by transferring mitochondria from lymphoblastoid cell lines derived from a Chinese family into
mitochondrial DNA(
mtDNA)-less (ρo) cells, we demonstrated the significant decreases in the efficiency of aminoacylation and steady-state level of mt-
tRNAAsp in mutant cybrids, compared with control cybrids. A failure in metabolism of mt-
tRNAAsp caused the variable reductions in
mtDNA-encoded
polypeptides in mutant cybrids. Impaired mitochondrial translation led to the respiratory phenotype in mutant cybrids. The respiratory deficiency lowed mitochondrial
adenosine triphosphate production and increased the production of oxidative reactive species in mutant cybrids. Our data demonstrated that
mitochondrial dysfunctions caused by the m.7551A > G mutation are associated with
deafness. Our findings may provide new insights into the pathophysiology of maternally transmitted
deafness that was manifested by altered
nucleotide modification of mitochondrial
tRNA.