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

A. Prelle, G. Fagiolari, N. Checcarelli, M. Moggio, A. Battistel, G. P. Comi, P. Bazzi, A. Bordoni, M. Zeviani, G. Scarlato

Research output: Contribution to journalArticlepeer-review

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 digoxygenin-labeled, polymerase chain reaction (PCR)-amplifed 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.

Original languageEnglish
Pages (from-to)371-376
Number of pages6
JournalActa Neuropathologica
Volume87
Issue number4
DOIs
Publication statusPublished - Apr 1994

Keywords

  • Immunohistochemistry
  • In situ hybridization
  • Mitochondrial myopathy
  • Ragged red fibers

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pathology and Forensic Medicine
  • Clinical Neurology

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