SENS5 - MitoSENS Allotopic expression of mitochondrial genes

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© SENS Foundation 2011 - http://www.sens.org

The Fifth SENS conference - Matthew O'Connor

SENS Foundation Research Center

Authors:
M.S. O'Connor, G. Swaminathan, S. Fazal, T. Jones, A.D.N.J. de Grey

The mitochondrion contains its own genome and encodes 13 proteins that are essential for the respiratory chain to function properly. Congenital mutations in many of the mitochondrial genes are the cause of serious disease phenotypes including diabetes, blindness, dementia, ataxia, epilepsy, and many other neurological disorders. Somatic mutations also accumulate in the mitochondria with normal aging. Allotopic expression of mitochondrial genes in the cell's nucleus is one approach to rescuing mitochondrial mutations. In our strategy, we utilize 5' and 3' elements to target mRNA to the outside surface of the mitochondria; this approach is a refinement of simple allotopic expression and is hypothesized to result in the co-translational import of the encoded proteins into the mitochondria. This approach is hypothesized to overcome obstacles (such as clogging of the mitochondrial import machinery by hydrophobic proteins) that many groups have experienced. Thus far, we have stably transfected 5 of the 13 mitochondrial genes into the nuclear genome of human cell lines and are characterizing the expression and function of these exogenously expressed genes. We will discuss current progress and future plans for replacing and/or making redundant the entire mitochondrial genome. We will also discuss potential applications of the MitoSENS approach in treating mitochondrial diseases, as well as the diseases and pathologies of aging.