Fly view of ROS and neurodegenerative disease

Mitochondrial dysfunction occurs in many late-onset neurodegenerative disorders (including Alzheimer's disease) and in developmental neurodegenerative disorders, such as Leigh syndrome, which is caused by mutations in the electron transport chain (ETC). But how does mitochondrial dysfunction cause neurodegeneration? Mast and co-workers perturbed the ETC in the Drosophila retina and now report that reactive oxygen species(ROS) overproduction in the photoreceptor cell body causes synaptic degeneration (see p. 2669). Mutations in the ETC component succinate dehydrogenase do not affect the early stages of photoreceptor development but cause degeneration of the photoreceptor synapses and cell bodies in late pupal and adult animals. ROS production, not energy depletion, causes this synaptic degeneration. Furthermore, ROS production in the cell body is sufficient to cause synaptic degeneration. These results establish the first animal model for Leigh syndrome and, more generally, suggest that excessive ROS production might cause some of the pathological changes seen in other neurodegenerative disorders.