Parkinson disease is characterized by the accumulation of aggregated α-synuclein 
as the major component of the Lewy bodies. α-Synuclein accumulation in turn 
leads to compensatory effects that may include the up-regulation of autophagy. 
Another common feature of Parkinson disease (PD) is mitochondrial dysfunction. 
Here, we provide evidence that the overactivation of autophagy may be a link 
that connects the intracellular accumulation of α-synuclein with mitochondrial 
dysfunction. We found that the activation of macroautophagy in primary cortical 
neurons that overexpress mutant A53T α-synuclein leads to massive mitochondrial 
destruction and loss, which is associated with a bioenergetic deficit and 
neuronal degeneration. No mitochondrial removal or net loss was observed when we 
suppressed the targeting of mitochondria to autophagosomes by silencing Parkin, 
overexpressing wild-type Mitofusin 2 and dominant negative Dynamin-related 
protein 1 or blocking autophagy by silencing autophagy-related genes. The 
inhibition of targeting mitochondria to autophagosomes or autophagy was also 
partially protective against mutant A53T α-synuclein-induced neuronal cell 
death. These data suggest that overactivated mitochondrial removal could be one 
of the contributing factors that leads to the mitochondrial loss observed in PD 
models.