Unusual pattern of mitochondrial DNA deletions in skeletal muscle of an adult human with chronic fatigue syndrome.

Genes in the 16.6 kb human mitochondrial DNA (mtDNA) are concerned exclusively with bioenergy production. Mutations in mtDNA can, therefore, lead to bioenergy decline and so contribute to various age-related degenerative diseases and even to 'natural' ageing (1-3). Large deletions in mtDNA occur in tissues of patients with mitochondrial myopathies and also occur in normal ageing, particularly in postmitotic tissues characterised by high energy demands and low rates of cell division, notably skeletal muscle, cardiac muscle and brain (4-11). The frequency in ageing of deletion-bearing mtDNA is much lower than that in overt mitochondrial diseases, but does regularly increase with advancing age. The age-associated deletions affecting mtDNA frequently include a 4977 bp deletion that is known as the 'common deletion' and is generated between a pair of 13 bp direct repeats, located at nucleotide (nt) positions 8470-8482 and nt 13447-13459, respectively (Table 1, Deletion 1). This deletion was detected by the polymerase chain reaction (PCR) in every postmitotic tissue examined, including skeletal muscle, heart and brain, from adult humans 40 years and over (4,7,13). In addition, a 7436 bp deletion, occurring between a pair of 12 bp direct repeats at nt 8637-8648 and nt 16073-16084 (Table 1, Deletion 2), has been observed in many adult postmitotic tissues, along with other deletions (2,6,9,14).