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

Vergani, Lodovica, Malena, Adriana, Sabatelli, Patrizia, Loro, Emanuele, Cavallini, Lucia, Magalhaes, Paolo, Valente, Lucia, Bragantini, Federica, Carrara, Franco, Leger, Bertrand, Poulton, Joanna, Russell, Aaron and Holt, Ian P. 2007, Cultured muscle cells display defects of mitochondrial myopathy ameliorated by anti-oxidants, Brain: a journal of neurology, vol. 130, no. 10, pp. 2715-2724.


Title Cultured muscle cells display defects of mitochondrial myopathy ameliorated by anti-oxidants
Author(s) Vergani, Lodovica
Malena, Adriana
Sabatelli, Patrizia
Loro, Emanuele
Cavallini, Lucia
Magalhaes, Paolo
Valente, Lucia
Bragantini, Federica
Carrara, Franco
Leger, Bertrand
Poulton, Joanna
Russell, Aaron
Holt, Ian P.
Journal name Brain: a journal of neurology
Volume number 130
Issue number 10
Start page 2715
End page 2724
Publisher Oxford University Press
Place of publication Oxford, England
Publication date 2007
ISSN 0006-8950
1460-2156
Keyword(s) cybrids
MELAS
differentiation
ROS
Summary 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.
Language eng
Field of Research 060105 Cell Neurochemistry
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2007, The Author
Persistent URL http://hdl.handle.net/10536/DRO/DU:30007522

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