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Cultured muscle cells display defects of mitochondrial myopathy ameliorated by anti-oxidants

journal contribution
posted on 01.01.2007, 00:00 authored by L Vergani, A Malena, P Sabatelli, E Loro, L Cavallini, P Magalhaes, L Valente, F Bragantini, F Carrara, B Leger, J Poulton, Aaron RussellAaron Russell, I Holt
The mitochondrial DNA A3243G mutation causes neuromuscular disease. To investigate the muscle-specific pathophysiology of mitochondrial disease, rhabdomyosarcoma transmitochondrial hybrid cells (cybrids) were generated that retain the capacity to differentiate to myotubes. In some cases, striated muscle-like fibres were formed after innervation with rat embryonic spinal cord. Myotubes carrying A3243G mtDNA produced more reactive oxygen species than controls, and had altered glutathione homeostasis. Moreover, A3243G mutant myotubes showed evidence of abnormal mitochondrial distribution, which was associated with down-regulation of three genes involved in mitochondrial morphology, Mfn1, Mfn2 and DRP1. Electron microscopy revealed mitochondria with ultrastructural abnormalities and paracrystalline inclusions. All these features were ameliorated by anti-oxidant treatment, with the exception of the paracrystalline inclusions. These data suggest that rhabdomyosarcoma cybrids are a valid cellular model for studying muscle-specific features of mitochondrial disease and that excess reactive oxygen species production is a significant contributor to mitochondrial dysfunction, which is amenable to anti-oxidant therapy.

History

Journal

Brain: a journal of neurology

Volume

130

Issue

10

Pagination

2715 - 2724

Publisher

Oxford University Press

Location

Oxford, England

ISSN

0006-8950

eISSN

1460-2156

Language

eng

Publication classification

C1 Refereed article in a scholarly journal

Copyright notice

2007, The Author