Mitochondrial DNA mutation-elicited oxidative stress, oxidative damage, and altered gene expression in cultured cells of patients with MERRF syndrome

Shi Bei Wu, Yi Shing Ma, Yu Ting Wu, Yin Chiu Chen, Yau Huei Wei*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

71 Scopus citations

Abstract

Myoclonic epilepsy and ragged-red fibers (MERRF) syndrome is a rare disorder characterized by myoclonus, muscle weakness, cerebellar ataxia, heart conduction block, and dementia. It has been documented that 80-90% of the patients with MERRF syndrome are caused by the A8344G mutation in the tRNALys gene of mitochondrial DNA (mtDNA). We and other investigators have reported that the mtDNA mutation results in not only inefficient generation of adenosine triphosphate but also increased production of reactive oxygen species (ROS) in cultured cells harboring A8344G mutation of mtDNA. In addition, we found an imbalance in the gene expression of antioxidant enzymes in the skin fibroblasts of MERRF patients. The mRNA, protein, and enzyme activity levels of manganese-superoxide dismutase were increased, but those of Cu,Zn-SOD, catalase, and glutathione peroxidase did not show significant changes. Recently, we showed that the excess ROS could damage voltage-dependent anion channel, prohibitin, Lon protease, and aconitase in the MERRF cells. Moreover, there was a dramatic increase in the gene expression and activity of matrix metalloproteinase 1, which may contribute to the cytoskeleton remodeling involved in the weakness and atrophy of muscle commonly seen in MERRF patients. Taken together, we suggest that mtDNA mutation-elicited oxidative stress, oxidative damage, and altered gene expression are involved in the pathogenesis and progression of MERRF syndrome.

Original languageEnglish
Pages (from-to)256-266
Number of pages11
JournalMolecular Neurobiology
Volume41
Issue number2-3
DOIs
StatePublished - 06 2010
Externally publishedYes

Keywords

  • Antioxidant enzyme
  • Lon protease
  • MERRF. Oxidative stress
  • MMP-1
  • Mitochondrial aconitase
  • Mitochondrial disease
  • Prohibitin

Fingerprint

Dive into the research topics of 'Mitochondrial DNA mutation-elicited oxidative stress, oxidative damage, and altered gene expression in cultured cells of patients with MERRF syndrome'. Together they form a unique fingerprint.

Cite this