Parkinson's disease (PD) is the second most common neurodegenerative disease. A 
key pathological feature of PD is Lewy bodies, of which the major protein 
component is α-synuclein (α-syn). Human genetic studies have shown that 
mutations (A53T, A30P, E46K) and multiplication of the α-syn gene are linked to 
familial PD. Mice overexpressing the human A53T mutant α-syn gene develop severe 
movement disorders. However, the molecular mechanisms of α-syn toxicity are not 
well understood. Recently, mitochondrial dysfunction has been linked with 
multiple neurodegenerative diseases including Parkinson's disease. Here we 
investigated whether mitochondrial motility, dynamics and respiratory function 
are affected in primary neurons from a mouse model expressing the human A53T 
mutation. We found that mitochondrial motility was selectively inhibited in A53T 
neurons while transport of other organelles was not affected. In addition, A53T 
expressing neurons showed impairment in mitochondrial membrane potential and 
mitochondrial respiratory function. Furthermore, we found that rapamycin, an 
autophagy inducer, rescued the decreased mitochondrial mobility. Taken together, 
these data demonstrate that A53T α-syn impairs mitochondrial function and 
dynamics and the deficit of mitochondrial transport is reversible, providing 
further understanding of the disease pathogenesis and a potential therapeutic 
strategy for PD.