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.

Instituto de Biología Celular y Neurociencias IBCN Facultad de Medicina Universidad de Buenos Aires Paraguay 2155 Buenos Aires CP1121 Argentina

Instituto de Biología y Medicina Experimental IBYME CONICET Vuelta de Obligado 2490 Buenos Aires CP1428 Argentina

International Clinical Research Center St Anne's University Hospital CZ 65691 Brno Czech Republic

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Intracellular and Intercellular Mitochondrial Dynamics in Parkinson's Disease

αSynuclein control of mitochondrial homeostasis in human-derived neurons is disrupted by mutations associated with Parkinson's disease