The effects of mitochondrial DNA damage on neurons

Obviously when mtDNA is damaged in neurons that can have various effects depending on the damage. A key point, however, is that if there is a process which is damaging mtDNA then if that continues then the mtDNA will get further damaged. As some relatively minor damage appears to be caused by the replication of mtDNA itself then it is like there is a very slow moving footpath moving towards cell failure. Hence when looking at how to rectify this then certain points need to be made.

1. When mtDNA is damaged this will not immediately affect the structure of the cell. What it does is to change how the cell produces or fails to produce proteins in the future. Hence if the process of mtDNA damage stops, the cell is unlikely to be in its stable state and can be expected to deteriorate in function to a point at which homeostasis is achieved.
2. It is hard, but possible, to improve mtDNA. However, that will not immediately improve the function of the cell and it may need a stimulus to regenerate a new homestasis.
3. Hence as the first thing is to stop the deterioration of mtDNA, this should not be expected to stop functional deterioration, but functional deterioration should stop at some point in the future.
4. As mtDNA deteriorates the systems that maintain mtDNA also deteriorate which means there is likely to be an accelerated rate of deterioration of mtDNA followed by functional deterioration.
5. Where you have a neuron with many axons even though mtDNA stops deterioration it is possible that some axons will continue to die off to a point at which the neuron can maintain the axonal arbour.

All of this points to the urgency of preventing damage to mtDNA (particularly deletions).