Mitochondrial myopathy: correlation between oxidative defect and mitochondrial DNA deletions at single fiber level.

TitleMitochondrial myopathy: correlation between oxidative defect and mitochondrial DNA deletions at single fiber level.
Publication TypeJournal Article
Year of Publication1994
AuthorsPrelle, A, Fagiolari, G, Checcarelli, N, Moggio, M, Battistel, A, Comi, GP, Bazzi, P, Bordoni, A, Zeviani, M, Scarlato, G
JournalActa Neuropathol
Volume87
Issue4
Pagination371-6
Date Published1994
ISSN0001-6322
KeywordsAdolescent, Adult, Aged, Cytochrome-c Oxidase Deficiency, DNA, Mitochondrial, Female, Gene Deletion, Humans, Immunohistochemistry, In Situ Hybridization, Male, Middle Aged, Mitochondrial Myopathies, Muscles, Nerve Fibers
Abstract

In situ hybridization combined with immunohistochemical techniques has been applied to study patients affected by mitochondrial myopathies with large mitochondrial (mt)DNA deletions. All patients' muscle biopsies showed ragged red fibers (RRFs) and cytochrome oxidase (COX) deficiency. Two digoxigenin-labeled, polymerase chain reaction (PCR)-amplified DNAs were used as probes. One probe was designed to hybridize only with wild-type mtDNAs, while the other recognized both wild-type and deleted mtDNAs. Concomitant immunocytochemical analysis using antibodies against subunits II, III, (encoded by mtDNA) and IV (encoded by nuclear DNA) of COX was carried out. In our patients deleted mtDNAs are overexpressed in COX-negative RRFs, while wild-type mtDNAs are decreased in the same fibers. Immunohistochemistry studies show that COX IV is overexpressed in RRFs and that COX II and COX III subunits are still present. Deleted mtDNAs are spatially segregated in muscle fibers, where they interfere with the local population of normal mitochondrial genomes, causing a regional deficiency of the mitochondrial respiratory activity.

DOI10.1007/bf00313606
Alternate JournalActa Neuropathol.
Citation Key10.1007/bf00313606
PubMed ID8017172