Mitochondrial dysfunction in a novel form of autosomal recessive ataxia

Murad, Nor Azian Abdul, 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 and Lavin, Martin F. (2013) Mitochondrial dysfunction in a novel form of autosomal recessive ataxia. Mitochondrion, 13 3: 235-245. doi:10.1016/j.mito.2012.11.006

Author Murad, Nor Azian Abdul
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.
Title Mitochondrial dysfunction in a novel form of autosomal recessive ataxia
Journal name Mitochondrion   Check publisher's open access policy
ISSN 1567-7249
Publication date 2013-05
Year available 2012
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1016/j.mito.2012.11.006
Open Access Status
Volume 13
Issue 3
Start page 235
End page 245
Total pages 11
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Collection year 2013
Language eng
Formatted 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.
Keyword Ataxia
DNA damage
Oculomotor apraxia type-2
Ocular motor apraxia
Oxidative stress
Apoptosis resistance
Protein aprataxin
Encoded subunits
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 21 November 2012

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: UQ Centre for Clinical Research Publications
Official 2013 Collection
School of Chemistry and Molecular Biosciences
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Citation counts: TR Web of Science Citation Count  Cited 4 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 3 times in Scopus Article | Citations
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Created: Wed, 13 Feb 2013, 10:33:11 EST by Mrs Maureen Pollard on behalf of Paediatrics & Child Health - RBWH