Single muscle fiber analysis of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes (MELAS)

Authors:
Publisher website
Google Scholar
Abstract
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.
Keywords

This publication has 25 references indexed in Scilit: