Neurons have a particularly high energy demand and are heavily dependent on a functional mitochondrial network. Mitochondria constantly engage in membrane fusion and fission cycles, in which single organelles frequently bud off or merge with the mitochondrial syncytium. The fragmentation of the mitochondrial network is one of the evolutionary conserved hall-mark events of apoptosis. In mammals inhibition of mitochondrial fission by disrupting of Drp1 function leads to a delay of cytochrome c release and consequently protects from apoptosis.
In contrast to mitochondria of Drp1-ablated mouse embryonic fibroblasts, mitochondria of Drp1-ablated neurons exhibit rather severe respiratory deficits. This aspect seems particularly important when treatment is targeted to more vulnerable neuronal subpopulations such as dopaminergic midbrain neurons, to prevent neuronal mitochondria from spherical enlargement and aggregation in perikarya.