The genetics of axonal mitochondrial biology
Mitochondria are essential in long axons to provide metabolic support and sustain neuron integrity. Hence deficits in mitochondrial function and mutations in mitochondrial regulating genes contribute to a wealth of neurodegenerative diseases. A healthy mitochondrial pool is maintained by a number of key processes including: biogenesis, transport, mitophagy, fission and fusion, but how these events are regulated in axons is not well defined. We hypothesised that there are a number of important genes that have not yet been identified and a comprehensive collection of conserved modulators of mitochondria in aged adult neurons is overdue. We therefore conducted an unbiased forwards genetic screen to find new genes that modulate mitochondria in axons in vivo, using Drosophila and verify our results using mammalian neurons in vitro . We present the identification and characterisation of several new mitochondrial target genes that alter mitochondrial size, number or distribution in axons. Functional characterisation of mitochondrial genes should provide exciting new insights into the molecular regulation of axon-mitochondrial interactions and are potential therapeutic targets for intervention in neurological disorders such as Alzheimer’s disease.