How discrete synaptic tissues cope with mitochondrial dysfunction

What is it about?

In this study, Mallik et al. impair mitochondrial function in a pair of synaptic tissues. Surprisingly, the tissues respond in starkly different ways. The model synapse is the fruit fly (Drosophila melanogaster) neuromuscular junction (NMJ). Mitochondria and cellular energy are important for neurotransmission. But the NMJ copes well when neuronal mitochondria are impaired. In the case of neuronal impairment, synapse function is normal because of a homeostatic upregulation in synaptic preactive zone materials. This homeostatic response is triggered by mitochondrial reactive oxygen species (ROS) that accumulate when the electron transport chain is interrupted. By contrast, when mitochondria are impaired on the muscle side of the NMJ, the postsynaptic density degrades, and NMJ development and function are greatly diminished. These loss-of-function phenotypes are also triggered by mitochondrial ROS. However, rather than a compensatory response, muscle mitochondrial ROS triggers a destructive response.

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Why is it important?

Mitochondrial dysfunction is associated with numerous neurological and neuromuscular conditions. By pinpointing how discrete tissues respond to mitochondrial dysfunction in a genetic model system, we have an opportunity to define cellular response mechanisms that are potentially relevant to disease.