Abstract
Mitochondrial electron transport chain (ETC) disorders cause severe neurological disease, typically in the context of fatal encephalomyelopathies. Neuronal cell autonomous energy deficiency due to reduced mitochondrial adenosine triphosphate production is currently the leading hypothesis to explain the neurotoxicity in ETC disorders. To define the mechanisms underlying neuropathology in ETC disorders, we have modeled the most common type of ETC disorder, complex I deficiency, in Drosophila. Our model recapitulates important clinical features of the disease including neuronal loss, mitochondrial enlargement, motor dysfunction and early death. Using cell-type specific gene knockdown, we find that both neurons and glia contribute to the disease phenotype and that glia play a critical non-cell autonomous role in the development of neuronal toxicity. Our results open up an unexpected avenue of research, and could lead to the development of new treatment strategies.