Stable nuclear expression of ATP8 and ATP6 genes rescues a mtDNA Complex V null mutant

摘要: We explore the possibility of re-engineering mitochondrial genes and expressing them from nucleus as an approach to rescue defects arising DNA mutations. have used a patient cybrid cell line with single point mutation in overlap region ATP8 ATP6 human genome. These cells are null for protein, significantly lowered protein levels no Complex V function. Nuclear expression only gene ATP5G1 targeting sequence appended restored viability on Krebs cycle substrates ATP synthesis capabilities but, failed restore hydrolysis was insensitive various inhibitors oxidative phosphorylation. Co-expressing both under similar conditions resulted stable leading successful integration into phosphorylation machinery. Tests / synthesis, oxygen consumption, glycolytic metabolism all indicate significant functional mutant phenotype (including re-assembly V) following co-expression Thus, we report allotopic expression, import function two mitochondria encoded genes, ATP6, resulting simultaneous loss proteins.