Single muscle fiber analysis of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS).
We examined muscle sections from 3 patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), using single-fiber polymerase chain reaction, histochemistry, and in situ hybridization. Most type 1 ragged-red fibers showed positive cytochrome c oxidase activity at the subsarcolemmal region, while type 2 ragged-red fibers had little cytochrome c oxidase activity. However, there was no difference in the amount of total (mutant and wild-type) mitochondrial DNAs (mtDNAs) and the proportion of mutant mtDNA between type 1 and type 2 ragged-red fibers. These observations suggest that mitochondrial proliferation and nuclear factors affect muscle pathology, including cytochrome c oxidase activity, in MELAS. Total mtDNAs were greatly increased in ragged-red fibers (about 5-17 times over those in non-ragged-red fibers). The proportion of mutant mtDNA was significantly higher in ragged-red fibers (88.1 +/- 5.5%) than in non-ragged-red fibers (63.2 +/- 21.6%). Thus, the amount of wild-type mtDNA as well as mutant mtDNA was increased in ragged-red fibers in MELAS, failing to support the contention of a replicative advantage of mutant mtDNA. The proportion of mutant mtDNA was significantly higher in the strongly succinate dehydrogenase-reactive blood vessels (83.2 +/- 4.2%) than in non-succinate dehydrogenase-reactive blood vessels (38.8 +/- 16.2%). It seems likely that systemic vascular abnormalities involving cerebral vessels lead to the evolution of stroke-like episodes in MELAS.
Tokunaga
M
M
First Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
Mita
S
S
Murakami
T
T
Kumamoto
T
T
Uchino
M
M
Nonaka
I
I
Ando
M
M
D001483:Base Sequence; D004272:DNA, Mitochondrial / Q000032:analysis*; D006801:Humans; D017403:In Situ Hybridization; D017241:MELAS Syndrome / Q000235:genetics* / Q000473:pathology*; D008969:Molecular Sequence Data; D009132:Muscles / Q000473:pathology*; D016133:Polymerase Chain Reaction
D004272:DNA, Mitochondrial