The organelles known as mitochondria play the role of power plant in the cell, generating energy stores to power cellular operations. As for all cellular components, mitochondria are built of proteins derived from DNA blueprints, but unlike all other cellular components mitochondria have their own DNA, separate from that in the cell nucleus. They are descendants of symbiotic bacteria, and continue to replicate like bacteria within our cells. Certain types of damage to mitochondrial DNA are one of the contributing causes of degenerative aging: mitochondria missing certain proteins become dysfunctional, ultimately taking over a small fraction of all cells by old age, and causing widespread harm in surrounding tissues.
In this paper researchers consider the process by which one bad mutation in one mitochondrion eventually fills the cell with duplicates of itself. This is one of the areas in which there is plenty of room for argument: does it happen because it confers the ability to replicate more readily, because it allows damaged mitochondria to evade quality control mechanisms, or for some other reason? As is often the case negative results in studies still add information to the overall picture:
Large-scale mitochondrial DNA (mtDNA) deletions are an important cause of mitochondrial disease, while somatic mtDNA deletions cause focal respiratory chain deficiency associated with ageing and neurodegenerative disorders. As mtDNA deletions only cause cellular pathology at high levels of mtDNA heteroplasmy, an mtDNA deletion must accumulate to levels which can result in biochemical dysfunction - a process known as clonal expansion. A number of hypotheses have been proposed for clonal expansion of mtDNA deletions, including a replicative advantage for deleted mitochondrial genomes inferred by their smaller size - implying that the largest mtDNA deletions would also display a replicative advantage over smaller mtDNA deletions.
We proposed that in muscle fibres from patients with mtDNA maintenance disorders, which lead to the accumulation of multiple mtDNA deletions, we would observe the largest mtDNA deletions spreading the furthest longitudinally through individual muscle fibres by means of a greater rate of clonal expansion. We characterized mtDNA deletions in patients with mtDNA maintenance disorders from a range of 'large' and 'small' cytochrome c oxidase (COX)-deficient regions in skeletal muscle fibres. We measured the size of clonally expanded deletions in 62 small and 60 large individual COX-deficient f regions. No significant difference was observed in individual patients or in the total dataset. Thus no difference existed in the rate of clonal expansion throughout muscle fibres between mtDNA deletions of different sizes; smaller mitochondrial genomes therefore do not appear to have an inherent replicative advantage in human muscle.