Hering, T;
Kojer, K;
Birth, N;
Hallitsch, J;
Taanman, JW;
Orth, M;
(2017)
Mitochondrial cristae remodelling is associated with disrupted OPA1 oligomerisation in the Huntington's disease R6/2 fragment model.
Experimental Neurology
, 288
pp. 167-175.
10.1016/j.expneurol.2016.10.017.
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Abstract
There is evidence of an imbalance of mitochondrial fission and fusion in patients with Huntington's disease (HD) and HD animal models. Fission and fusion are important for mitochondrial homeostasis including mitochondrial DNA (mtDNA) maintenance and may be relevant for the selective striatal mtDNA depletion that we observed in the R6/2 fragment HD mouse model. We aimed to investigate the fission/fusion balance and the integrity of the mitochondrial membrane system in cortex and striatum of end-stage R6/2 mice and wild-type animals. Mitochondrial morphology was determined using electron microscopy, and transcript and protein levels of factors that play a key role in fission and fusion, including DRP1, mitofusin 1 and 2, mitofilin and OPA1, and cytochrome c and caspase 3 were assessed by RT-qPCR and immunoblotting. OPA1 oligomerisation was evaluated using blue native gels. In striatum and cortex of R6/2 mice, mitochondrial cristae morphology was abnormal. Mitofilin and the overall levels of the fission and fusion factors were unaffected; however, OPA1 oligomerisation was abnormal in striatum and cortex of R6/2 mice. Mitochondrial and cytoplasmic cytochrome c levels were similar in R6/2 and wild-type mice with no significant increase of activated caspase 3. Our results indicate that the integrity of the mitochondrial cristae is compromised in striatum and cortex of the R6/2 mice and that this is most likely caused by impaired OPA1 oligomerisation.
| Type: | Article |
|---|---|
| Title: | Mitochondrial cristae remodelling is associated with disrupted OPA1 oligomerisation in the Huntington's disease R6/2 fragment model |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.expneurol.2016.10.017 |
| Publisher version: | http://dx.doi.org/10.1016/j.expneurol.2016.10.017 |
| Language: | English |
| Additional information: | Copyright © 2016 Elsevier Inc. All rights reserved.This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Caspase 3, Cristae integrity, Fission and fusion, Mitofilin, OPA 1 oligomerisation |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1530691 |
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