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Mitochondrial dysfunction in a novel form of autosomal recessive ataxia
journal contributionposted on 2013-05-01, 00:00 authored by Nor Azian Abdul Murad, Jason K Cullen, Matthew McKenzieMatthew McKenzie, Michael T Ryan, David Thorburn, Nuri Gueven, Junya Kobayashi, Geoff Birrell, Jian Yang, Thilo Dörk, Olivier Becherel, Padraic Grattan-Smith, Martin F Lavin
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.
Pagination235 - 245
LocationAmsterdam, The Netherlands
Publication classificationC1.1 Refereed article in a scholarly journal
Copyright notice2012, Elsevier B.V.
AtaxiaMitochondriaDNA damageAmino Acid SubstitutionAnimalsChromosome DisordersCytochromes bDNA Mutational AnalysisDNA, MitochondrialElectron TransportMembrane Potential, MitochondrialMitochondrial DiseasesMutation, MissenseOxidative StressProtein StabilityReactive Oxygen SpeciesTumor Suppressor Protein p53Science & TechnologyLife Sciences & BiomedicineCell BiologyGenetics & HeredityOCULOMOTOR APRAXIA TYPE-2OCULAR MOTOR APRAXIADNA-DAMAGEAPOPTOSIS RESISTANCEPROTEIN APRATAXINENCODED SUBUNITSCOMPLEX-ITELANGIECTASIAMUTATIONS