An Allotopic Expression Update

From the SENS Foundation, an update on allotopic expression of mitochondrial DNA - the SENS approach to eliminating the contribution of mitochondrial DNA damage to aging. Vulnerable but essential mitochondrial genes are copied into the protected cell nucleus, and one of a variety of strategies are then used to ensure the encoded proteins get back to the mitochondria where they are needed: "To date, three of the thirteen OXPHOS genes still encoded in the mitochondria have been allotopically expressed (AE) in human cells ... In work funded by SENS Foundation, Corral-Debrinski's group have used their improved AE technique of relocalizing translation of AE genes to the mitochondrial surface [to] reverse blindess in rats caused by exposure to mutations in this gene ... Now we have the first report of a new gene, COX2, being allotopically expressed in yeast, by mutating the gene to overcome the hydrophobicity of the mitochondrial membrane ... This is an exciting advance [and] the first allotopic expression of this respiratory chain component in a species in which evolution has never accomplished the feat for itself. The next step, of course, is to do it in mammalian cells - preferably, of our own species. And the same broad strategy likely applies to many of the other remaining [thirteen genes of interest]; indeed, during his work sponsored by SENS Foundation, Mark Hamalainen developed software that models hydrophobicity of proteins, and it predicts that a relatively small number of relatively minor amino acid changes would lower the hydrophobicity [sufficiently] to make them importable when the native gene likely is not."



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