Using our optimized micropatterned substrates we found that alterations of mitochondrial parameters change over time in normal healthy dopaminergic neurons; e.g. an increase in mitochondrial length and interconnectivity as well as a reduction in anterograde transport towards more stationary mitochondria from day 40 to day 100 of differentiation. It is well established that adaptations in mitochondrial dynamics are required during development and aging to maintain mitochondrial function, but the precise nature of these changes has not been studied in human neurons [42]. Fusion and fission events are mediated through different specialized proteins (reviewed in [43]). While fission events have been shown to be preceded by a sustained fall in mitochondrial membrane potential [44], fusion mixes mitochondrial contents and is known to benefit mtDNA stability and allows the spreading of metabolites, enzymes, and mitochondrial gene products throughout the mitochondrial compartment and also serves to repair abnormal mitochondrial phenotypes [45]. The extensive fusion of mitochondria observed at later time points in our studies might indicate a compensatory response to mitochondrial damage. Hyperfused mitochondria may be resistant to apoptosis [46] and escape autophagosomal
