THE EFFECT ON MITOCHONDRIAL-FUNCTION OF THE TRNA(SER(UCN)) COI A7445GMTDNA POINT MUTATION ASSOCIATED WITH MATERNALLY-INHERITED SENSORINEURAL DEAFNESS/

An A to G point mutation at nucleotide position 7445 in the mitochondr ial DNA genome is associated with maternally-inherited sensorineural d eafness in two separate human pedigrees. To determine whether this poi nt mutation [tRNA(Ser(UCN))/COI A7445G] led to sensorineural deafness by affecting cellular energy metabolism we investigated the bioenerget ic function of mitochondria in lymphoblastoid cultures established fro m these patients. Even though essentially all of the mitochondrial DNA in these cells contained the mutation at nucleotide position 7445, th ere was no effect on a number of mitochondrial bioenergetic functions (mitochondrial content, membrane potential in both intact and digitoni n-permeabilised cells, cellular ATP/ADP ratios and respiratory enzyme activity) when compared with control cells. The implications of these findings for both the aetiology of the sensorineural deafness associat ed with the A7445G mtDNA mutation, and the role of bioenergetic defect s in mitochondrial DNA diseases in general, an discussed.