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Aggregated a-synuclein and complex I deficiency: exploration of their relationship in differentiated neurons

Reeve, A K; Ludtmann, M H R; Angelova, P R; Simcox, E M; Horrocks, M H; Klenerman, D; Gandhi, S; Turnbull, D M; Abramov, A Y

Authors

A K Reeve

M H R Ludtmann

P R Angelova

E M Simcox

M H Horrocks

D Klenerman

S Gandhi

D M Turnbull

A Y Abramov



Abstract

α-Synuclein becomes misfolded and aggregated upon damage by various factors, for example, by reactive oxygen species. These aggregated forms have been proposed to have differential toxicities and their interaction with mitochondria may cause dysfunction within this organelle that contributes to the pathogenesis of Parkinson’s disease (PD). In particular, the association of α-synuclein with mitochondria occurs through interaction with mitochondrial complex I and importantly defects of this protein have been linked to the pathogenesis of PD. Therefore, we investigated the relationship between aggregated α-synuclein and mitochondrial dysfunction, and the consequences of this interaction on cell survival. To do this, we studied the effects of α-synuclein on cybrid cell lines harbouring mutations in either mitochondrial complex I or IV. We found that aggregated α-synuclein inhibited mitochondrial complex I in control and complex IV-deficient cells. However, when aggregated α-synuclein was applied to complex I-deficient cells, there was no additional inhibition of mitochondrial function or increase in cell death. This would suggest that as complex I-deficient cells have already adapted to their mitochondrial defect, the subsequent toxic effects of α-synuclein are reduced.

Citation

Reeve, A. K., Ludtmann, M. H. R., Angelova, P. R., Simcox, E. M., Horrocks, M. H., Klenerman, D., …Abramov, A. Y. (2015). Aggregated a-synuclein and complex I deficiency: exploration of their relationship in differentiated neurons. https://doi.org/10.1038/cddis.2015.166

Journal Article Type Article
Acceptance Date May 19, 2015
Publication Date Jul 16, 2015
Deposit Date Jun 28, 2018
Publicly Available Date Mar 28, 2024
Journal CELL DEATH & DISEASE
Peer Reviewed Peer Reviewed
Volume 6
Pages e1820
DOI https://doi.org/10.1038/cddis.2015.166
Public URL https://rvc-repository.worktribe.com/output/1400188

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