Nuclear expression of mitochondrial ND4 leads to the protein assembling in complex I and prevents optic atrophy and visual loss

摘要: Leber hereditary optic neuropathy is due to mitochondrial DNA mutations; in ~70% of all cases, a point mutation the NADH dehydrogenase subunit 4, ND4, gene leads central vision loss. We optimized allotopic expression (nuclear transcription that normally transcribed inside mitochondria) aimed at designing therapy for ND4; its coding sequence was associated with cis-acting elements human COX10 mRNA allow efficient delivery protein. After ocular administration adult rats recombinant adeno-associated viral vector containing ND4 gene, we demonstrated that: (i) sustained did not lead harmful effects, instead protein efficiently imported mitochondria and assembled respiratory chain complex I; (ii) presence experimental model significantly prevents retinal ganglion cell degeneration preserves both I function nerves visual function. Hence, use relevant treating disorders mutations organelle genome.