Foti, S;
Hargreaves, I;
Carrington, S;
Kiely, AP;
Houlden, H;
Holton, J;
(2019)
Cerebral mitochondrial electron transport chain dysfunction in multiple system atrophy and Parkinson’s disease.
Scientific Reports
, 9
, Article 6559. 10.1038/s41598-019-42902-7.
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Abstract
Multiple system atrophy (MSA) is a neurodegenerative disease characterised by glial cytoplasmic inclusions (GCIs), containing α-synuclein. Mutated COQ2, encoding an enzyme essential for co-enzyme Q10 (CoQ10) biosynthesis, has been associated with MSA. CoQ10 is an electron carrier in the mitochondrial electron transport chain (ETC) and antioxidant. It has been shown to be deficient in MSA brain tissue, thus implicating mitochondrial dysfunction in MSA. To investigate mitochondrial dysfunction in MSA further we examined ETC activity in MSA and control brain tissue, compared with Parkinson’s disease (PD) where mitochondrial dysfunction is known to be important. Using cerebellar and occipital white matter ETC complex I, II/III and IV activities were measured spectrophotometrically, selected individual components of the ETC were assessed by immunoblotting and cellular complex IV activity was analysed by enzyme histochemistry. We show decreased complex II/III activity with increased complex I and IV activity in MSA cerebellar white matter. This corresponds with the deficit in CoQ10 previously described in MSA and reflects the high regional pathological burden of GCIs. This study highlights mitochondrial dysfunction in MSA pathogenesis, suggests an influence on selective regional vulnerability to disease and points to shared disease mechanisms in α-synucleinopathies.
| Type: | Article |
|---|---|
| Title: | Cerebral mitochondrial electron transport chain dysfunction in multiple system atrophy and Parkinson’s disease |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41598-019-42902-7 |
| Publisher version: | https://doi.org/10.1038/s41598-019-42902-7 |
| Language: | English |
| Additional information: | Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| 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 > Department of Neuromuscular Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UK Dementia Research Institute HQ |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10072779 |
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