One of the causes of aging is mitochondrial DNA damage. The mitochondria, the cell's herd of bacteria-like power plants, contain their own DNA, separate from that in the cell nucleus. It is more vulnerable to damage: mitochondrial DNA repair mechanisms are not as good as those operating in the nucleus, and mitochondria generate reactive free radical molecules in the course of their operation.
DNA provides the blueprints for protein machinery, and some forms of damage to mitochondrial DNA can lead to crippled mitochondria that can nonetheless out-compete their undamaged brethren. Cells become taken over by broken mitochondria and themselves begin to malfunction and harm surrounding tissue: by the time you are old this is a very significant issue that contributes to a range of fatal age-related conditions. Yet this can all be reversed provided that the necessary proteins are provided to the mitochondria. There are numerous strategies, some more permanent than others: the SENS Research Foundation favors a one-time life-long fix that puts copies of mitochondrial genes into the cell nucleus, for example. But more temporary solutions include delivering the proteins directly, or delivering extra copies of undamaged mitochondrial DNA to swamp out the damaged copies and provide the necessary protein blueprints.
A number of ways are either proposed or demonstrated to deliver new DNA to mitochondria, and here is another of them. As is usually the case, the focus here is on comparatively rare genetic disorders rather than the ubiquitous problem of aging, however:
Mitochondrial genetic disorders are a major cause of mitochondrial diseases. It is therefore likely that mitochondrial gene therapy will be useful for the treatment of such diseases. Here, we report on the possibility of mitochondrial gene delivery in skeletal muscle using hydrodynamic limb vein (HLV) injection. The HLV injection procedure, a useful method for transgene expression in skeletal muscle, involves the rapid injection of a large volume of naked plasmid DNA (pDNA) into the distal vein of a limb.
We hypothesized that the technique could be used to deliver pDNA not only to nuclei but also to mitochondria, since cytosolic pDNA that is internalized by the method may be able to overcome mitochondrial membrane. We determined if pDNA could be delivered to myofibrillar mitochondria by HLV injection by PCR analysis. These findings indicate that HLV injection promises to be a useful technique for in vivo mitochondrial gene delivery.