Zen and the art of mitochondrial DNA maintenance

Because mitochondrial genes encode proteins essential for aerobic ATP production, mitochondrial DNA defects can cause an energy crisis. These defects fall into two broad categories: primary mutations in mitochondrial DNA and mutations in nuclear genes, whose protein products are involved in mitochondrial DNA maintenance. Evidence is accumulating that both types of defects can cause mitochondrial DNA loss. Hence, regulatory factors, which determine whether mitochondrial DNA molecules are maintained or lost, potentially play a more important role in these disorders than hitherto recognised. Candidates include reactive oxygen species (ROS) and the tumour suppressor p53. The cell might not always be the best judge of when to dispense with the services of mitochondrial DNA, and so interventions that favour its retention could potentially limit the adverse effects of pathological mitochondrial DNAs.