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Genetics of Axonal Mitochondrial Biology

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Maintaining healthy mitochondrial populations in axons is essential to sustain neuronal function, and represents a major challenge for neurons given the relative size of axons, which in humans can be up to meter long. Consequently, deficits in mitochondrial function contribute to a wealth of neurodegenerative diseases, where axonal die back often precedes cell body demise. We know relatively little about the basic biology of axonal mitochondrial delivery, maintenance and function in vivo. Here we describe novel, genome-wide unbiased F1 forward genetic screen in Drosophila for modifiers of mitochondrial populations in axons. We used the MARCM approach to fluorescently label homozygous mutants clones of glutamatergic sensory neurons and the mitochondria they contain, in the translucent adult Drosophila wing. This system allowed for the rapid assay mitochondrial morphology, number, and distribution in axons with single axon and single mitochondrion resolution. We have discovered several mitochondrial mutants that exhibit dramatic changes in mitochondria number and/or size.

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