Allotopic expression of mitochondrial-encoded genes in mammals: achieved goal, undemonstrated mechanism or impossible task?

ABSTRACT: Mitochondrial-DNA diseases have no effective treatments. Allotopic expression-synthesis of a wild-type version of the mutated protein in the nuclear-cytosolic compartment and its importation into mitochondria-has been proposed as a gene-therapy approach. Allotopic expression has been successfully demonstrated in yeast, but in mammalian mitochondria results are contradictory. The evidence available is based on partial phenotype rescue, not on the incorporation of a functional protein into mitochondria. Here, we show that reliance on partial rescue alone can lead to a false conclusion of successful allotopic expression. We recoded mitochondrial mt-Nd6 to the universal genetic code, and added the N-terminal mitochondrial-targeting sequence of cytochrome c oxidase VIII (C8) and the HA epitope

SUBMITTER: Perales-Clemente E 

PROVIDER: S-EPMC3017613 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature