Mitochondrial dysfunction in a novel form of autosomal recessive ataxia

Nor Azian Abdul Murad, Jason K. Cullen, Matthew McKenzie, Michael T. Ryan, David Thorburn, Nuri Gueven, Junya Kobayashi, Geoff Birrell, Jian Yang, Thilo Dörk, Olivier Becherel, Padraic Grattan-Smith, Martin F. Lavin

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Defects in the recognition and/or repair of damage to DNA are responsible for a sub-group of autosomal recessive ataxias. Included in this group is a novel form of ataxia with oculomotor apraxia characterised by sensitivity to DNA damaging agents, a defect in p53 stabilisation, oxidative stress and resistance to apoptosis. We provide evidence here that the defect in this patient's cells is at the level of the mitochondrion. Mitochondrial membrane potential was markedly reduced in cells from the patient and ROS levels were elevated. This was accompanied by lipid peroxidation of mitochondrial proteins involved in electron transport and RNA synthesis. However, no gross changes or alteration in composition or activity of mitochondrial electron transport complexes was evident. Sequencing of mitochondrial DNA revealed a mutation, I349T, in the mitochondrial cytochrome b gene. These results describe a patient with an apparently novel form of AOA characterised by a defect at the level of the mitochondrion.

Original languageEnglish
Pages (from-to)235-245
Number of pages11
JournalMitochondrion
Volume13
Issue number3
DOIs
Publication statusPublished - May 2013

Fingerprint

Ataxia
Electron Transport
Mitochondria
Cytochromes b
Mitochondrial Membrane Potential
Mitochondrial Proteins
Mitochondrial DNA
Lipid Peroxidation
DNA Damage
Oxidative Stress
RNA
Apoptosis
Mutation
DNA
Genes

Keywords

  • Ataxia
  • DNA damage
  • Mitochondria

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Molecular Medicine

Cite this

Abdul Murad, N. A., Cullen, J. K., McKenzie, M., Ryan, M. T., Thorburn, D., Gueven, N., ... Lavin, M. F. (2013). Mitochondrial dysfunction in a novel form of autosomal recessive ataxia. Mitochondrion, 13(3), 235-245. https://doi.org/10.1016/j.mito.2012.11.006

Mitochondrial dysfunction in a novel form of autosomal recessive ataxia. / Abdul Murad, Nor Azian; Cullen, Jason K.; McKenzie, Matthew; Ryan, Michael T.; Thorburn, David; Gueven, Nuri; Kobayashi, Junya; Birrell, Geoff; Yang, Jian; Dörk, Thilo; Becherel, Olivier; Grattan-Smith, Padraic; Lavin, Martin F.

In: Mitochondrion, Vol. 13, No. 3, 05.2013, p. 235-245.

Research output: Contribution to journalArticle

Abdul Murad, NA, Cullen, JK, McKenzie, M, Ryan, MT, Thorburn, D, Gueven, N, Kobayashi, J, Birrell, G, Yang, J, Dörk, T, Becherel, O, Grattan-Smith, P & Lavin, MF 2013, 'Mitochondrial dysfunction in a novel form of autosomal recessive ataxia', Mitochondrion, vol. 13, no. 3, pp. 235-245. https://doi.org/10.1016/j.mito.2012.11.006
Abdul Murad, Nor Azian ; Cullen, Jason K. ; McKenzie, Matthew ; Ryan, Michael T. ; Thorburn, David ; Gueven, Nuri ; Kobayashi, Junya ; Birrell, Geoff ; Yang, Jian ; Dörk, Thilo ; Becherel, Olivier ; Grattan-Smith, Padraic ; Lavin, Martin F. / Mitochondrial dysfunction in a novel form of autosomal recessive ataxia. In: Mitochondrion. 2013 ; Vol. 13, No. 3. pp. 235-245.
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