ABSTRACT
The distinctive pathological hallmarks of Parkinson's disease are the progressive death of dopaminergic neurons and the intracellular accumulation of Lewy bodies enriched in α-synuclein protein. Several lines of evidence from the study of sporadic, familial and pharmacologically induced forms of human Parkinson's disease also suggest that mitochondrial dysfunction plays an important role in disease progression. Although many functions have been proposed for α-synuclein, emerging data from human and animal models of Parkinson's disease highlight a role for α-synuclein in the control of neuronal mitochondrial dynamics. Here, we review the α-synuclein structural, biophysical and biochemical properties that influence relevant mitochondrial dynamic processes such as fusion-fission, transport and clearance. Drawing on current evidence, we propose that α-synuclein contributes to the mitochondrial defects that are associated with the pathology of this common and progressive neurodegenerative disease.
Footnotes
This article is part of a special subject collection ‘Neurodegeneration: from Models to Mechanisms to Therapies’, which was launched in a dedicated issue guest edited by Aaron Gitler and James Shorter. See related articles in this collection at http://dmm.biologists.org/collection/neurodegenerative-disorders.
Competing interests
The authors declare no competing or financial interests.
Funding
This work was supported by grants from Agencia Nacional de Promoción Científica y Tecnológica [PICT 2011-2027; PICT 2013-0402 to T.L.F.], from the University of Buenos Aires (Universidad de Buenos Aires) [UBACyT and PDTS to T.L.F.], CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), and by the European Social Fund and European Regional Development Fund – Project MAGNET (Number CZ.02.1.01/0.0/0.0/15_003/0000492). V.M.P.D. was a recipient of a postdoctoral fellowship from CONICET and a travelling fellowship from the Company of Biologists, publisher of DMM.
- Received June 29, 2017.
- Accepted July 13, 2017.
- © 2017. Published by The Company of Biologists Ltd
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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