Alpha-synuclein impairs normal dynamics of mitochondria in cell and animal models of Parkinson's disease

J. Neurochem. (2012) 122, 404414. Abstract Alpha-synuclein (a-syn) is a synaptic protein that mutations have been linked to Parkinsons disease (PD), a common neurodegenerative disorder that is caused by the degeneration of the dopaminergic neurons in the substantia nigra pars compacta (SNc). How a-syn can contribute to neurodegeneration in PD is not conclusive but it is agreed that mutations or excessive accumulation of a-syn can lead to the formation of a-syn oligomers or aggregates that interfere with normal cellular function and contribute to the degeneration of dopaminergic neurons. In this study, we found that a-syn can impair the normal dynamics of mitochondria and this effect is particular prominent in A53T a-syn mutant. In mice expressing A53T a-syn, age-dependent changes in both mitochondrial morphology and proteins that regulate mitochondrial fission and fusion were observed. In the cellular model of PD, we found that a-syn reduces the movement of mitochondria in both SH-SY5Y neuroblastoma and hippocampal neurons. Taken together, our study provides a new mechanism of how a-syn can contribute to PD through the impairment of normal dynamics of mitochondria.