Journal Article

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

Lodovica Vergani, Adriana Malena, Patrizia Sabatelli, Emanuele Loro, Lucia Cavallini, Paolo Magalhaes, Lucia Valente, Federica Bragantini, Franco Carrara, Bertrand Leger, Joanna Poulton, Aaron P. Russell and Ian J. Holt

in Brain

Published on behalf of The Guarantors of Brain

Volume 130, issue 10, pages 2715-2724
Published in print October 2007 | ISSN: 0006-8950
Published online July 2007 | e-ISSN: 1460-2156 | DOI:
Cultured muscle cells display defects of mitochondrial myopathy ameliorated by anti-oxidants

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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.

Keywords: Cybrids; MELAS; Differentiation; ROS

Journal Article.  5803 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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