Mitochondrial Function in Axotomy-Induced Axon Degeneration
Authors:
Mauricio Vargas, Nickolas WheatMentor:
Alvaro Sagasti, Associate Professor of Molecular, Cell, and Developmental Biology, University of California Los AngelesAxon degeneration is a common endpoint for multiple neurodegenerative diseases, including diabetic neuropathy, stroke, and traumatic injury. Although mitochondrial mechanisms regulating cell body death are well understood, their role in axon degeneration is largely unknown. Uncoupling mitochondrial oxidative phosphorylation leads to decreased production of reactive oxygen species and adenosine triphosphate (ATP). Our hypothesis is that mitochondrial oxidative phosphorylation instructively regulates axon degeneration. Our lab has developed a model to study axon degeneration in live zebrafish using laser axotomy (axon severing). Axon degeneration after this type of injury is called Wallerian degeneration and is conserved throughout vertebrates and invertebrates. Time lapse movies of axotomized zebrafish axons using confocal microscopy were created after uncoupling oxidative phosphorylation using two techniques: treating zebrafish embryos with a chemical mitochondrial uncoupling agent or overexpressing mitochondrial uncoupler protein-2 (UCP2) with specific enhancers that drive expression of this protein to sensory neurons. Surprisingly, preliminary results suggest that uncoupling oxidative phosphorylation has no effect on the rate of Wallerian degeneration. However, further experiments are underway to test more rigorously whether oxidative phosphorylation inhibits the rate of axon degeneration. Understanding how mitochondria are involved in Wallerian degeneration may identify mechanisms involved in other forms of axon degeneration.