DISTRIBUTION OF WILD-TYPE AND COMMON DELETION FORMS OF MTDNA IN NORMAL AND RESPIRATION-DEFICIENT MUSCLE-FIBERS FROM PATIENTS WITH MITOCHONDRIAL MYOPATHY

We studied the cellular distribution of both deleted (Delta) and wild-type (wt) mitochondrial DNAs (mtDNAs) in 'normal' and respiration-deficient muscle fibers from four patients with mitochondrial myopathy. pop-based methods were used to quantitate both relative and absolute amounts of Delta- and wt-mtDNAs in microdissected fiber segments. Although Delta-mtDNAs were present in normal fibers(31% +/- 26), their percentages were much higher in affected fibers (95% +/- 2). Absolute levels of Delta-mtDNA were also increased in affected fibers, whereas levels of wt-mtDNA were significantly reduced in these fibers. These results indicate that a threshold ratio of Delta-/wt-mtDNA must be achieved before an impairment of respiration is observed in muscle. Moreover, the marked reduction in wt-mtDNA observed in affected fibers suggests that absolute amounts of mtDNA may play a role in the pathogenesis of mitochondrial myopathies.